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The Quinolones Past Present and Future
Vincent T AndrioleYale University School of Medicine New Haven Connecticut
Unlike some of the first antibiotics discovered during the past century the quinolone class of antimicrobial agents was not isolated from living
organisms but rather was synthesized by chemists
Chemical structure of the quinolonenaphthyridone ring system showing sites that are modified in various agents and the structures of the fluoroquinolones investigated
Pestova E et al J Antimicrob Chemother 200045583-590
copy 2000 The British Society for Antimicrobial Chemotherapy
Atomo di fluoro in posizione 6
FARMACOCINETICA CHINOLONI
In early studies the quinolones were observed to have excellent oral absorption good distribution in tissue with excellent interstitial fluid levels entry into phagocytic cells and urinary concentrations that exceeded the MICs for many common pathogens Key structural modifications resulted in improved pharmacokinetics (eg a longer elimination half-life which permitted once-daily dosing and better tissue penetration) of some of the newest quinolones including gatifloxacin gemifloxacin grepafloxacin moxifloxacin sitafloxacin sparfloxacin and trovafloxacin Specific modifications included alkylation of the quinolones which improved elimination half-life and penetration into tissue the addition of 2 methyl groups to the C-7 piperazine ring which increased oral efficacy the addition of an amino group at C-5 which increased lipophilicity and the addition of a halogen at position C-8 which improved in vivo activity
Clinical Infectious Diseases 2005 41S113ndash9
I chinoloni sono divisi in quattro generazioni in base al loro spettro di azioneQuelli delle prime generazioni sono quelli con uno spettro di azione piugrave ristretto
1a generazione
CinoxacinaAcido nalidissicoAcido ossolinicoAcido piromidicoAcido piemidicoRosoxacina
2a generazione
CiprofloxacinaEnoxacinaFleroxacina
LomefloxacinaNadifloxacinaNorfloxacinaOxafloxacina
3a generazione
GatifloxacinaGrepafloxacinaSparfloxacina
4a generazione
ClinafloxacinaGarenoxacinaGemifloxacinaSitafloxacina
Trovafloxacina
Spettro di azione dei chinolonici
1deg GenerazioneAcido nalidissico Escherichia coli Proteus Shigella Enterobacter e Klebsiella
2deg GenerazioneCiprofloxacina Come quelli della prima generazione ed nei confronti della salmonella typhy
3deg GenerazioneGatifloxacina Chlamydophila pneumoniae e Mycoplasma pneumoniae
4deg GenerazioneGemifloxacina Moraxella catarrhalis Acinetobacter lwoffii Klebsiella oxytoca Legionella pneumophila Proteus vulgaris - Chlamydia pneumoniae Mycoplasma pneumoniae
2a Generazione
2a Generazione
3a Generazione
4a Generazione
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Chemical structure of the quinolonenaphthyridone ring system showing sites that are modified in various agents and the structures of the fluoroquinolones investigated
Pestova E et al J Antimicrob Chemother 200045583-590
copy 2000 The British Society for Antimicrobial Chemotherapy
Atomo di fluoro in posizione 6
FARMACOCINETICA CHINOLONI
In early studies the quinolones were observed to have excellent oral absorption good distribution in tissue with excellent interstitial fluid levels entry into phagocytic cells and urinary concentrations that exceeded the MICs for many common pathogens Key structural modifications resulted in improved pharmacokinetics (eg a longer elimination half-life which permitted once-daily dosing and better tissue penetration) of some of the newest quinolones including gatifloxacin gemifloxacin grepafloxacin moxifloxacin sitafloxacin sparfloxacin and trovafloxacin Specific modifications included alkylation of the quinolones which improved elimination half-life and penetration into tissue the addition of 2 methyl groups to the C-7 piperazine ring which increased oral efficacy the addition of an amino group at C-5 which increased lipophilicity and the addition of a halogen at position C-8 which improved in vivo activity
Clinical Infectious Diseases 2005 41S113ndash9
I chinoloni sono divisi in quattro generazioni in base al loro spettro di azioneQuelli delle prime generazioni sono quelli con uno spettro di azione piugrave ristretto
1a generazione
CinoxacinaAcido nalidissicoAcido ossolinicoAcido piromidicoAcido piemidicoRosoxacina
2a generazione
CiprofloxacinaEnoxacinaFleroxacina
LomefloxacinaNadifloxacinaNorfloxacinaOxafloxacina
3a generazione
GatifloxacinaGrepafloxacinaSparfloxacina
4a generazione
ClinafloxacinaGarenoxacinaGemifloxacinaSitafloxacina
Trovafloxacina
Spettro di azione dei chinolonici
1deg GenerazioneAcido nalidissico Escherichia coli Proteus Shigella Enterobacter e Klebsiella
2deg GenerazioneCiprofloxacina Come quelli della prima generazione ed nei confronti della salmonella typhy
3deg GenerazioneGatifloxacina Chlamydophila pneumoniae e Mycoplasma pneumoniae
4deg GenerazioneGemifloxacina Moraxella catarrhalis Acinetobacter lwoffii Klebsiella oxytoca Legionella pneumophila Proteus vulgaris - Chlamydia pneumoniae Mycoplasma pneumoniae
2a Generazione
2a Generazione
3a Generazione
4a Generazione
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
FARMACOCINETICA CHINOLONI
In early studies the quinolones were observed to have excellent oral absorption good distribution in tissue with excellent interstitial fluid levels entry into phagocytic cells and urinary concentrations that exceeded the MICs for many common pathogens Key structural modifications resulted in improved pharmacokinetics (eg a longer elimination half-life which permitted once-daily dosing and better tissue penetration) of some of the newest quinolones including gatifloxacin gemifloxacin grepafloxacin moxifloxacin sitafloxacin sparfloxacin and trovafloxacin Specific modifications included alkylation of the quinolones which improved elimination half-life and penetration into tissue the addition of 2 methyl groups to the C-7 piperazine ring which increased oral efficacy the addition of an amino group at C-5 which increased lipophilicity and the addition of a halogen at position C-8 which improved in vivo activity
Clinical Infectious Diseases 2005 41S113ndash9
I chinoloni sono divisi in quattro generazioni in base al loro spettro di azioneQuelli delle prime generazioni sono quelli con uno spettro di azione piugrave ristretto
1a generazione
CinoxacinaAcido nalidissicoAcido ossolinicoAcido piromidicoAcido piemidicoRosoxacina
2a generazione
CiprofloxacinaEnoxacinaFleroxacina
LomefloxacinaNadifloxacinaNorfloxacinaOxafloxacina
3a generazione
GatifloxacinaGrepafloxacinaSparfloxacina
4a generazione
ClinafloxacinaGarenoxacinaGemifloxacinaSitafloxacina
Trovafloxacina
Spettro di azione dei chinolonici
1deg GenerazioneAcido nalidissico Escherichia coli Proteus Shigella Enterobacter e Klebsiella
2deg GenerazioneCiprofloxacina Come quelli della prima generazione ed nei confronti della salmonella typhy
3deg GenerazioneGatifloxacina Chlamydophila pneumoniae e Mycoplasma pneumoniae
4deg GenerazioneGemifloxacina Moraxella catarrhalis Acinetobacter lwoffii Klebsiella oxytoca Legionella pneumophila Proteus vulgaris - Chlamydia pneumoniae Mycoplasma pneumoniae
2a Generazione
2a Generazione
3a Generazione
4a Generazione
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
I chinoloni sono divisi in quattro generazioni in base al loro spettro di azioneQuelli delle prime generazioni sono quelli con uno spettro di azione piugrave ristretto
1a generazione
CinoxacinaAcido nalidissicoAcido ossolinicoAcido piromidicoAcido piemidicoRosoxacina
2a generazione
CiprofloxacinaEnoxacinaFleroxacina
LomefloxacinaNadifloxacinaNorfloxacinaOxafloxacina
3a generazione
GatifloxacinaGrepafloxacinaSparfloxacina
4a generazione
ClinafloxacinaGarenoxacinaGemifloxacinaSitafloxacina
Trovafloxacina
Spettro di azione dei chinolonici
1deg GenerazioneAcido nalidissico Escherichia coli Proteus Shigella Enterobacter e Klebsiella
2deg GenerazioneCiprofloxacina Come quelli della prima generazione ed nei confronti della salmonella typhy
3deg GenerazioneGatifloxacina Chlamydophila pneumoniae e Mycoplasma pneumoniae
4deg GenerazioneGemifloxacina Moraxella catarrhalis Acinetobacter lwoffii Klebsiella oxytoca Legionella pneumophila Proteus vulgaris - Chlamydia pneumoniae Mycoplasma pneumoniae
2a Generazione
2a Generazione
3a Generazione
4a Generazione
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Spettro di azione dei chinolonici
1deg GenerazioneAcido nalidissico Escherichia coli Proteus Shigella Enterobacter e Klebsiella
2deg GenerazioneCiprofloxacina Come quelli della prima generazione ed nei confronti della salmonella typhy
3deg GenerazioneGatifloxacina Chlamydophila pneumoniae e Mycoplasma pneumoniae
4deg GenerazioneGemifloxacina Moraxella catarrhalis Acinetobacter lwoffii Klebsiella oxytoca Legionella pneumophila Proteus vulgaris - Chlamydia pneumoniae Mycoplasma pneumoniae
2a Generazione
2a Generazione
3a Generazione
4a Generazione
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
2a Generazione
2a Generazione
3a Generazione
4a Generazione
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
2a Generazione
3a Generazione
4a Generazione
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
3a Generazione
4a Generazione
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Mechanismo di Azione
I chinoloni sono farmaci battericidi
Inibiscono la DNA girasi batterica detta anche topoisomerasi IV inibendo cosigrave la replicazione e la trascrizione del DNA batterico
I chinoloni entrano nel batterio attraverso dei canali detti porine e perciograve vengono usati nel trattare infezioni batteriche di patogeni che si replicano
allrsquointerno di cellule umane quali la legionella ed il micoplasma pneumonie
Per molti batteri gram negativi la DNA girasi egrave il target di questi antibatterici mentre per molti gram positivi il target egrave la DNA topoisomerasi IV
Le cellule eucariotiche non contengono ne DNA girasi e ne DNA topoisomerasi IV
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Effetto dellaDNA girasi
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Gli effetti collaterali dei fluorochinoloni possono essere di natura lieve e di breve durata o di natura severa e di lunga durata dopo che la terapia egrave stata terminata
Se gli effetti collaterali avvengono al livello del Sistema nervoso centrale (SNC) o del sistema nervoso periferico (SNP) o a livello del sistema muscolare la terapia deve essere interrotta immediatamente
Gli effetti collaterali dei fluorochinoloni sono i seguenti Ansietagrave dolore articolare dolore muscolare tendiniti visione offuscata perdita della memoria diarrea attacchi di panico insonnia rottura del tendine drsquoachille tachicardia
Effetti collaterali dei fluorochinoloni
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Adverse events commonly associated with the fluoroquinolones include gastrointestinal and CNS toxicity (most frequently headache and dizziness) as well as other adverse events including ECG abnormalities (for example QT interval prolongation) disrupted glucose metabolism phototoxicity tendon and joint disorders hypersensitivity and skin disorders and hepatic toxicity
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Expert Opin Drug Saf 2012 Jan11(1)53-69 Epub 2011 Sep 30Cardiovascular and metabolic safety profiles of the fluoroquinolonesPugi A Longo L Bartoloni A Rossolini GM Mugelli A Vannacci A Lapi FUniversity of Florence Department of Pharmacology Viale Pieraccini 6 50139 Florence Italy francescolapiunifiit
INTRODUCTION Certain fluoroquinolones share similar indications of use A comparison among Cardiovascular and metabolic (ie dysglycemia) safety profiles of the fluoroquinolones might be particularly useful for the prescribers decision-making process as well as to hypothesize future researcher purposes
EXPERT OPINION Cardiac alterations and blood glucose impairments might be associated with any fluoroquinolone However the benefitrisk profile of these agents could be stratified for the single compounds Several predisposing factors such as diabetes heart illnesses and their related pharmacotherapies might exacerbate the risk of potentially serious adverse events
In this context the opportunity of the more appropriate choice among different fluoroquinolones could be applicable
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
We did find however an interaction between the combined use of fluoroquinolones and reninndashangiotensin-system blockers
CMAJ July 9 2013 185(10)
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
J Antimicrob Chemother 1986 Nov18 Suppl D187-93Ciprofloxacin an overview of adverse experiencesBall PAbstractThis review summarizes adverse reactions probably or possibly attributable to oral ciprofloxacin therapy in worldwide clinical experience involving over 6500 patients In Europe and Japan the overall incidence of adverse reactions amongst patients receiving ciprofloxacin is reported to be 30 and 65 respectively An increased incidence (134) has been reported from the USA possibly relating to the use of higher dosages Very few reactions have necessitated withdrawal of treatment The most common adverse effects involve the gastro-intestinal system (2-8 of patients treated) and usually comprise nausea vomiting diarrhoea and abdominal discomfort CNS effects are seen in 1-4 of patients but are usually minor dizziness or mild headache only Hypersensitivity reactions most commonly skin rashes or pruritus affect about 1 of patients There is little evidence of significant haematological or biochemical toxicity other than a few reports of transient neutropenia and the finding in a minority of clinical studies of equally transient usually trivial and invariably reversible elevations of serum aminotransferases Serious ciprofloxacin-related toxicity has been observed in only three patients one who developed pseudomembranous colitis another who developed interstitial nephritis and a third who had a grand-mal convulsion during concomitant administration of theophylline Ciprofloxacin appears to have an excellent safety profile
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Macrolidi
I macrolidi sono un gruppo di farmaci la cui attivitagrave risiede nella sua struttura macrolide The most important macrolide antibiotics are 14- 15- and 16-membered compounds I classici farmaci macrolidi sono
1) Eritromicina2) Claritromicina3) Azitromicina4) Roxitromicina5) Telitromicina6) Spiramicina
Eritromicina
ClaritromicinaThe molecular structure of erythromycin the 14- membered prototype macrolide
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Azitromicina
Azithromycin and to a lesser extent clarithromycin are noted for their high and prolonged concentrations at sites of infection reaching tissue levels of 10ndash100-fold and 2ndash20- fold greater than serum concentrations respectively
Both agents are also concentrated intracellularly by alveolar macrophages attaining levels of approximately 400-fold (clarithromycin) and 800-fold (azithromycin) above serum concentrations
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Drug delivery problems resulting from acid instability prompted the design of newer macrolides
These compounds include (i)clarithromycin roxithromycin dirithromycin and the ketolides and fluoroketolides all of which have a 14-membered ring structure (ii) the 15-membered azithromycin and (iii) the 16-membered agents spiramycin rokitamycin and josamycin
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Macrolide antibiotics are generally used to treat respiratory and soft tissue infections caused by Gram-positive bacteria
They are also active against rickettsiae chlamydiae and Mycoplasma pneumoniae
as well as some Gram-negative bacterial pathogens including Bacteroides fragilis Bordetella pertussis Campylobacter species Haemophilus influenzaeHelicobacter pylori Legionella pneumophila Moxarella catarrhalis and Neisseria species
Spettro drsquoAzione
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Le subunitagrave ribosomiali dei batteri e degli eucarioti sono simili
I batteri hanno unrsquounitagrave ribosomiale 70S che consiste di una subunitagrave 30S
(composta da RNA di 1540 nucleotidi e 21 proteine) e una 50S (che consiste di due
subunitagrave di RNA di 2900 + 120 nucleotidi e 34 proteine)
I Ribosomi
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Meccanismo di azione
I macrolidi inibiscono la crescita batterica interferendo nella loro sintesi proteica I macrolidi si legano alla subunitagrave 50s
ribosomiale inibendo la sintesi peptidica
Sintesi proteica
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
I macrolidi sono usati per trattare le faringiti tonsilliti
sinusiti bronchiti polmoniti infezioni cutanee di
malati di AIDS Possono anche essere usai nei casi
di legionella
Usi terapeutici
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Paragoni di MIC tra macrolidi
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Effetti Collaterali
Lrsquoeffetto collaterale piugrave comune nei macrolidi egrave la diarrea con nausea dolore addominale e vomito
Gli effetti meno comuni sono mal di testa rash cutanei e alterazione del gusto
Gli effetti piugrave gravi sono itterizia e insufficienza renale
ControindicazioniLa claritromicina non deve essere usata in casi di soggetti con epatopatie e ridotta funzionalitagrave renale Inoltre in alcuni pazienti puograve portare al prolungamento del QT
bradicardia o riduzione dei livelli di potassio e magnesioLa claritromicina interagisce con molti farmaci e quindi deve essere considerata una
possibile riduzioneaumento dellrsquoativitagrave di questi farmaci
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Clarithromycin inhibits the middle to late stage of the influenza virus
replication cycle resulting in inhibition of progeny virus production
from the infected cells Macrolides could mediate this effect by
inhibiting intracellular hemagglutinin HA0 proteolisis
The inhibitory effects on influenza virus replication of macrolides has
been known since the 80s and have been observed for other
viruses such as Sindibis virus
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Resistance to macrolides in S pneumoniae is mediated by 2 major mechanisms
1) target modification caused by a ribosomal methylase encoded by the erm(B) geneor 2) drug efflux encoded by the mef(A) gene High-levelmacrolide resistance (MIC required to inhibit growth in90 of organisms [MIC90] gt32 μgmL) is usually associatedwith erm(B) whereas mef(A)-mediated resistance themost prevalent mechanism in the United States usuallyresults in lower-level resistance (MIC90 1ndash4 μgmL)
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Cochrane Database Syst Rev 2004(4)CD001954 Azithromycin for acute lower respiratory tract infectionsPanpanich R Lerttrakarnnon P Laopaiboon M
Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia There is unclear evidence that azithromycin is superior to amoxicillin or amoxyclav in treating acute LRTI In patients with acute bronchitis of a suspected bacterial cause azithromycin tends to be more effective in terms of lower incidence of treatment failure and adverse events than amoxicillin or amoxyclav
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Le lincosamidi (es lincomicina clindamicina) sono una classe di farmaci che legano la porzione 23s della subunitagrave 50s dei batteri ribosomi inibendo il prolungamento del peptide attraverso lrsquoinibizione della reazione di trans-peptidizzazione
Lincosamidi
Lincomicina Clindamicina
Spettro drsquoazione antimicrobico
La lincomicina possiede lo stesso spettro drsquoazione antimicrobico della claritromicina
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Continua
Macrolide Lincosamidi e streptogramine (MLS) antibiotici
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Streptogramine
Le Streptogramine sono degli antibiotici battericidi appartenenti a due categorie
1)Streptogramina A Dalfopristina
2) Streptogramina B Quintupristina
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Streptogramina A Streptogramina B
dalfopristina
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Le streptogramine vengono somministrate insieme
in un rapporto 3070 Esse inibiscono la sintesi
proteica in maniera sinergistica La quinupristina si
lega alla subunitagrave 50s prevenendo lrsquoallungamento
della catena peptidica mentre la dalfopristina si lega
ad un sito vicino alla subunitagrave 50s ribosomiale
aumentando il legame della quinupristina al
ribosoma
Meccanismo di azione
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Quinupristinadalfopristina (Synercid) sono la combinazione dei due antibiotici Viene usata per trattare le infezioni da staphylococci e da batteri resistenti alla vancomycina
Non sono efficaci nelle infezioni da Enterococcus faecalis
Usi terapeutici
Effetti collaterali
Dolore articolari e muscolari nausea vomito e diarreaRash cuanei
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Le Tetracicline sono degli antibiotici a largo spettro drsquoazione prodotti dal genus streptomices degli actinobatteri
Tetracicline
They are broad-spectrum antibiotics effective against aerobic and anaerobic Gram-positive and Gram-negative bacteria as well as Richettsia Mycoplasma Chlamydia spp and Legionella spp
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Tetracicline in terapia
1)Minociclina2)Doxiciclina3)Demeclociclina4)oxitetraciclina
Spettro drsquoazione antibatterica 1) Neisserie gonorreae2) Clamidia3) Bacillus antracis4) Yersinia pestis5) Richettsie (tifo)6) Brucella7) Treponema
Meccanismo di azione
Le tetracicline sono una famiglia di antibiotici che inibiscono il legame dellrsquoRNA
transfer alla subunitagrave ribosomiale 30s del batterio Sono batteriostatiche
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
They inhibit bacterial protein synthesis by binding to the 30S bacterial ribosome and preventing access of aminoacyl tRNA to the acceptor (A) site on the mRNA-ribosome complex
Tetracyclines can also cause alterations in the cytoplasmic membrane leading to leakage of nucleotides and other compounds from the bacterial cell
At higher concentrations tetracycline may inhibit protein synthesis inmammalian cells
Doxycycline and minocycline are semi-synthetic derivatives of tetracycline These two compounds are more lipid soluble which gives them some advantages over tetracycline hydrochloride such as a lower dosage regimen prolonged serum half-life super tissue fluid penetration and decreased gastrointestinal side-effects
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Resistenza batterica alle tetracicline
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Cautele Controindicazioni ed effetti collaterali Le tetracicline possono macchiare I denti in fase di sviluppo nei bambini Le tetracicline sono inattivate dagli ioni Ca++ Al3+ Fe2+ e Zn2+ presenti
nel latte e nei cibiSono inattivate dai comuni farmaci antiacidi
Danno fotosensibilitagrave quindi deve essere evitata lrsquoesposizione al solePossono dare lupus eritematosus epatiti e tinniti
Tetracicline e gravidanza-allattamento
Le tetracicline non possono essere somministrate in donne gravide sia per
problemi vero il feto che verso la madre (epatopatia) Le tetracicline
passano nel latte materno percui sono da evitare anche nellrsquoallattamento
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
PubMed-MEDLINE and EMBASE databases (1974ndashMarch 2009) reviewedreference citations from identified publications researched antibioticprescribing information and corresponded with drug manufacturers Casereports case series and both in vivo and in vitro clinical trials were evaluatedfor the following antibiotics clindamycin daptomycin linezolid quinupristindalfopristinrifampin tetracycline doxycycline minocycline tigecycline trimethoprim-sulfamethoxazole and vancomycin Information for the newer antibiotics (linezolid quinupristin-dalfopristin tigecycline and daptomycin)was limited Despite heterogeneity in the data for the older antibiotics(clindamycin rifampin tetracyclines trimethoprim-sulfamethoxazole andvancomycin) all appear to be relatively safe in the minimal quantities nursinginfants ingest through breast milk Although the risk to infants seems to berelatively low for most of the agents we explored the paucity of data indicates a need for close monitoring of breastfed infants whose mothers are receiving an antibiotic for an MRSA skin and soft tissue infection
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Expert Opin Investig Drugs 2010 February 19(2) 215ndash234
Nuovi recenti farmaci approvati dallFDA
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Linezolid
Linezolid is a synthetic antibiotic the first of the oxazolidinone class used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA)
The drug works by inhibiting the initiation of bacterial protein synthesis
Meccanismo di azione
Oxazolidinoni
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Glycylcyclines are the newest member in the tetracycline class ofantibacterial drugs and one member (tigecycline) was approved by the FDA (June 2005) 5 for complicated skin and skin structure infections and also for intra-abdominal infection
The novelty about glycylcyclines is their ability to subvert the common tetracycline resistance mechanisms acquired by genetically mobile element encoding the tet genes The two major resistance mechanisms are tetracycline efflux pumps or ribosomal protection The compound with t-butylglycylamido moiety at position 9 of minocycline (tigecycline) exhibits potent antibacterial activity and also potency against tetracycline resistant bacteria
Mechanism of Action
The glycylcyclines bind with a 5-fold to 100-fold higher affinity to 30S and and 70S ribosomes respectively than tetracyclines and also inhibit protein synthesis of Tet(M) and Tet(O) tetracycline resistant bacteria Protein synthesis inhibition by tigecycline is 20-fold more efficient than tetracycline
Glicilcicline
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
tigecycline
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
Ann Pharmacother 2013 Mar47(3)368-79 Cethromycin a new ketolide antibioticMansour H Chahine EB Karaoui LR El-Lababidi RMSourceCollege of Pharmacy University of Florida FL USA Haninemansourlauedulb
AbstractOBJECTIVETo review the pharmacology chemistry microbiology in vitro susceptibility mechanism of resistance pharmacokinetics pharmacodynamics clinical efficacy safety drug interactions dosage and administration of cethromycin a new ketolide antibioticDATA SOURCESLiterature was obtained through searching PubMed (1950-October 2012) International Pharmaceutical Abstracts (1970-October 2012) and a bibliographic review of published articles Search terms included cethromycin ABT-773 ketolide antibiotic and community-acquired pneumoniaSTUDY SELECTION AND DATA EXTRACTIONAll available in vitro and preclinical studies as well as Phase 1 2 and 3 clinical studies published in English were evaluated to summarize the pharmacology chemistry microbiology efficacy and safety of cethromycin in the treatment of respiratory tract infectionsDATA SYNTHESISCethromycin a new ketolide has a similar mechanism of action to telithromycin with an apparently better safety profile Cethromycin displays in vitro activity against selected gram-positive gram-negative and atypical bacteria The proposed indication of cethromycin is treatment of mild to moderate community-acquired bacterial pneumonia in patients aged 18 years or older Based on clinical studies the recommended dose is 300 mg orally once a day without regard to meals Cethromycin has an orphan drug designation for tularemia plague and anthrax prophylaxis The Food and Drug Administration denied approval for the treatment of community-acquired pneumonia in 2009 a recent noninferiority trial showed comparable efficacy between cethromycin and clarithromycin Preliminary data on adverse effects suggest that cethromycin is safe and gastrointestinal adverse effects appear to be dose-relatedCONCLUSIONSCethromycin appears to be a promising ketolide for the treatment of mild to moderate community-acquired pneumonia It was denied approval by the FDA in 2009 pending more evidence to show its efficacy with more recent studies showing its noninferiority to antibiotics for the same indication
PMID 23463743
