CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
Selectively inhibit bacterial protein synthesis Protein synthesis in microorganisms is not
identical to mammalian cells 70S ribosomes in bacteria 80S ribosomes in mammalians
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
Basis for selective toxicity against microorganisms without causing major effects on mammalian cells Differences
Ribosomal subunits Chemical composition Functional specificities of component nucleic
acids and proteins
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
BACTERIAL PROTEIN SYNTHESIS INHIBITORS
BROAD SPECTRUM MODERATE SPECTRUM NARROW SPECTRUM
CHLORAMPHENICOL MACROLIDES KETOLIDES LINCOSAMIDES
TETRACYCLINES STREPTOGRAMINS
LINEZOLID
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MECHANISM OF ACTION Bacteriostatic inhibitors of protein synthesis 50S ribosome unit
Except of tetracycline
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MECHANISM OF ACTION Chloramphenicol
Inhibits transpeptidation (catalyzed by peptidyl transferase)
Blocks the binding of aminoacyl moiety of tRNA to mRNA complex peptide at the donor site cannot be transferred to the amino acid acceptor
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MECHANISM OF ACTION Macrolides, telithromycin, and clindamycin
Bind at 50S-block translocation of peptidyl-tRNA from the acceptor site to the donor site
tRNA cannot access the occupied receptor site, it is not added to the peptide chain
http://pharmacologycorner.com/protein-synthesis-inhibitors-macrolides-mechanism-of-action-animation-classification-of-agents/
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MECHANISM OF ACTION Tetracyclines
Bind to 30S Blocks the binding of amino-acid-charged
tRNA to the acceptor site http://pharmacologycorner.com/protein-synthesis-
inhibitors-tetracyclines-mechanism-of-action-animation-classification-of-agents/
Tetracyclines and
Chloramphenicol
Tetracyclines
Antimicrobia activitybroad spectrum antibiotics: effective against a large no of
organisms: Atypical organisms (like Chlamydia spp, Legionella spp, Rickettsiae,
Mycoplasma pneumoniae) Some atypical mycobacteria Camplylobacter jejuni Helicobacter pylori. A variety of gram-positive, gram-negative organisms: vibrio cholerae,
plague, tularemia, brucellosis. For protozoal infection- E. Histolytica, P.falciparum. Effective against many anaerobes (doxycycline)
ClassificationOlder tetracyclines: 1. Short acting (half life 6 hours)-Tetracycline,
chlortetracycline, oxytetracycline2. Intermediate acting- half life 16 hours-
demeclocyclineNewer ones :3. Long acting – half life-18-24 hours- doxycycline
and minocycline are more lipophilic and most active.
4. Longest acting: Tigecycline- newest – half life-36 hours
Tetracyclines Mechanism of action Bacteriostatic agents. Inhibit protein synthesis via reversible
binding to 30 s ribosome, block the binding of aminoacyl tRNA to the acceptor site on mRNA. This prevents addition of aminoacid to growing polypeptide.
Resistance : Dec. accumulation due to dec. influx, or inc. efflux. Dec. access to ribosome due to presence of ribosome protection proteins Enzymatic inactivation of tetracycline
ADME of tetracyclinesAbsorption: Doxycycline & minocycline- 100%. Food does not
interfere with their abs. Abs. of others is dec. by concurrent adm. of dairy
products alum, Ca++, Mg, Bi & iron salts- due to chelation of divalent or trivalent cations.
Distribution Protein binding 40-80% Conc. in liver, exc. in int. via bile-EHC. Widely distributed in tissues except CSF- On I.V:
appear in spinal fluid. Tetracyclines cross placenta High conc. found in breast milk.
Metabolism Minocycline, doxycycline and tigecycline –metabolized in liver. Doxycycline is exc. in feces- preferred to treat extra renal infection in
patients with renal failure. Enzyme inducers dec. their half lives.
ExcretionAll tetracyclines are exc. in urine and feces (bile).
Precautions Pregnancy, lactation and in children 8 years. In patients with renal or hepatic disease Don’t use expired preparations.
Adverse effects of tetracylines
I Gastrointestinal. (Dose dependent GI irritation)II Photosensitivity: sunburn, onycholysis & pigmentation of
nailsIII. Hepatic toxicity: with Large oral or IV doses esp. in
pregnant women – hepatic necrosis.IV.Effect on bones and teeth: Brown discoloration of the teeth
(milk (from mid pregnancy to 6 months postnatally & permanent- aged- 2 M- 5 years). 40% dec. in bone growth-
V Superinfection
Uses
DOC for infections produced by : chlamydiae; rickettsia; mycoplasma, legionella infections. Vibrio cholera. In combination with aminoglycosides: plague, brucellosis, tularemia.
Other uses: Exacerbation of chronic bronchitis CAP Treatment of acne & skin infections. Tetracycline for eradication of H.pylori Doxycycline: lyme disease (1st choice); and prophylaxis of
chloroquine resistant P. falciparum malaria
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESA. CLASSIFICATION Structural congeners Broad range of antimicrobial activity Minor differences in activity against organisms
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESB. PHARMACOKINETICS Oral absorption is variable especially for older
drugs Impaired by food and multivalent cations
Calcium, iron and aluminum Wide tissue distribution Cross the placental barrier
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESB. PHARMACOKINETICS Enterohepatic cycling All drugs eliminated in the urine
Doxycycline Excreted in the feces
Together with minocycline have longer half-lives
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESC. ANTIBACTERIAL ACTIVITY Gram (+) and gram (-) bacteria
Rickettsia Chlamydia Mycoplasma Some protozoa
Organisms accumulate the drug intracellularly via energy-dependent transport systems
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESC. ANTIBACTERIAL ACTIVITY Plasmid-mediated resistance is widespread
Decrease activity of the uptake systems Development of efflux pumps for active
extrusion of the drug
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESD. CLINICAL USES1. Primary uses Tetracyclines
M. pneumoniae (in adults) Chlamydia Rickettsia Vibrio cholera
Drug of choice
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLIDTETRACYCLINESD. CLINICAL USES2. Secondary uses Tetracyclines
Alternative drug for syphilis Respiratory infections caused by susceptible
organisms Prophylaxis against chronic bronchitis Leptospirosis Treatment of acne
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESD. CLINICAL USES3. Selective uses Tetracycline
Gastrointestinal ulcers caused by H. pylori Doxycycline
Lyme disease
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESD. CLINICAL USES3. Selective uses Minocycline
Meningococcal carrier state Doxycycline
Prevention of malaria Treatment of amoebiasis
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESD. CLINICAL USES3. Selective uses Demeclocycline
ADH-secreting tumors Inhibits renal actions of ADH
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESE. TOXICITY1. GI disturbances Mild nausea and diarrhea to severe, possibly
life-threatening colitis Disturbances in the normal flora
Candidiasis (oral and vaginal) Bacterial superinfection
S. aureus or C. difficile Rare
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESE. TOXICITY2. Bony structures and teeth Fetal exposure
Tooth enamel dysplasia Irregularities in bone growth
Contraindicated in pregnancy
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESE. TOXICITY2. Bony structures and teeth Younger children (under age 8)
Enamel dysplasia and crown deformation when permanent teeth appears
Bind with calcium and deposit in newly formedbones (impaired long bone formation ) and teeth(discolouration of teeth)
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESE. TOXICITY3. Hepatic toxicity High doses in pregnant women and
those with preexisting renal disease may impair liver function
Hepatic necrosis
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESE. TOXICITY4. Renal toxicity Fanconi’s syndrome
Renal tubular acidosis Intake of outdated tetracycline
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TETRACYCLINESE. TOXICITY3. Photosensitivity Demeclocycline
Enhanced skin sensitivity to ultraviolet light4. Vestibular toxicity Doxycycline and minocycline
Dose-dependent reversible dizziness and vertigo
Tigecycline
Effective against: Certain tetracycline resistant strains of organisms; MRSA; vancomycin resistant staph; VREnterococci, Strep (penicillin susceptible & resistant); G+ve rods; enterobacteriaceae; multidrug resistant acinetobacter spp; anaerobes (G+ve, G-ve); atypical agents: rickettisiae, chlamydia, legionella, rapidly growing mycobacteria.
Proteus and pseudomonas are intrinsically resistant.
Uses Multidrug resistant nosocomial pathogens (MRSA, extended
spectrum beta lactamase producing G –ve organisms & acinetobacter spp.
Treatment of skin & skin structure infections & intraabdominal infections. Not for UTI (not effective conc in urine).
ChloramphenicolMechanism of action Inhibits protein synthesis, binds reversibly
to 50 S ribosomal subunit, prevents binding of aminoacyl tRNA to 50 S ribosomes, inhibits peptidyl transferase step in protein synthesis.
Also inhibits mitochondrial protein synthesis by acting on 70 S ribosome- mammalian erythropoietic cells are particularly sensitive to the drug.
Bacteriostatic, bactericidial for H.influanzae, N.meningitidis & S.pneumoniae
Antimicrobial spectrum: broad spectrum (G + ve & –ve orga. aerobes and most anaerobes)
Effective against H. influenzae, N. meningitidis, Salmonella typhi, Brucella species, Bordetella pertussis & anaerobes- highly susceptible.
Effective against Rickettsiae, Mycoplasma & Chlamydia.
Resistance to chloramphenicol: Acetylation of chloramphenicol due to plasmid
encoded acetyl transferase. Acetylated drug fails to bind to bacterial ribosomes.
Dec. permeability of the microorganisms (E. Coli).
ChloramphenicolADME Well absorbed orally. Distributed in body fluids- CSF conc. 60%, crosses
placental barrier & aqueous humor. Metabolized in the liver by glucuronidation by
glucuronyl transferase. Drug interactions
Irreversible inhibition of CYP P450 leads to inc. half-life of warfarin, phenytoin, tolbutamide, etc.
Enzyme inducers (rifampin, phenobarbitone) shorten the T ½ of chloramphenicol.
Adverse effects1. Hematological toxicity:
i Idiosyncratic reaction (dose independent)- aplastic anemia: leukopenia, thrombocytopenia & aplasia of marrow. May be fatal or may lead to acute myeloblastic leukemia later on.
ii A 2nd dose related hematological effect: reversible suppression of bone marrow with conc. > 25 g/ml.
iii. Hemolytic anemia in G6PD deficiency2. Toxic and irritable effects
Fatal chloramphenicol toxicity (conc >100 g/ml) - in neonate esp. in premature - called "gray baby syndrome" -due to failure of glucuronidation (lack of glucuronyl transferase in first 3-4 weeks of life, & dec. renal function)
Optic neuritis, peripheral neuritis. 3. Hypersensitivity reactions. 4. GI disturbances: N,V, D.5. Superinfection: oral or vaginal candidiasis due to alteration of normal
flora.
Therapeutic uses
Because of potential toxicity, bacterial resistance & availability of effective alternative drugs, it is rarely used. Should never be used for minor infections, or infections which could be treated by other drugs.
Second choice drug in 1 Typhoid fever:2. Bacterial meningitis. 3. rickettsial infection and4. Anaerobic infection- Brain abscess. 5. Intraocular infection6. Topical use: conjunctivitis and external ear infections.
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLA. CLASSIFICATION Simple and distinctive structure No other antimicrobials in this class Oral as well as parenteral Distributed throughout all tissues Crosses placental and blood-brain barriers
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLA. CLASSIFICATION Enterohepatic cycling Fraction excreted in urine unchanged Inactivated by hepatic glucoronosyltransferase
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLB. ANTIMICROBIAL ACTIVITY Bacteriostatic Bactericidal for some strains
H. influenzae N. meningitidis Bacteroides
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLB. ANTIMICROBIAL ACTIVITY Not effective for chlamydia Resistance
Plasmid mediated-formation of acetyl- transferases that inactivate the drug
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLC. CLINICAL USES Few uses as systemic drug because of toxicity Backup drug for severe infections caused by
salmonella Treatment of pneumococcal and meningococcal
meningitis in beta-lactam-sensitive persons
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLC. CLINICAL USES Sometimes used for ricketssial infections Infections caused by anaerobes like B. fragilis Commonly used as topical agent
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLD. TOXICITY1. GI disturbances Direct irritation and superinfection
Candidiasis
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLD. TOXICITY2. Bone marrow Inhibition of red cell maturation decrease
in circulating RBC Reversible
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLD. TOXICITY3. Aplastic anemia Rare idiosyncratic reaction Irreversible and maybe fatal
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CHLORAMPHENICOLD. TOXICITY4. Gray baby syndrome Premature infants Deficiency of hepatic glucoronyltransferase Tolerated in older infants Decreased RBC, cyanosis and cardiovascular
collapse
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MECHANISM OF ACTION Streptogramins
Bactericidal Bind to 50S Constrict the exit channel on the ribosome
through which polypeptides are extruded tRNA synthase activity is inhibited
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MECHANISM OF ACTION Linezolid
Bacteriostatic Binds to a unique site at 50S Blocks formation of tRNA-ribosome-
mRNA complex
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESA. CLASSIFICATION AND PHARMACOKINETICS Erythromycin , azithromycin, and clarithromycin
Large cyclic lactone ring structure with attached sugars
Good oral bioavailability Distribute to most body tissues
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESA. CLASSIFICATION AND PHARMACOKINETICS Azithromycin
Absorption is impeded by food Levels in tissues and phagocytes are higher
than in plasma Eliminated slowly in the urine mainly as
unchanged drug Half-life is 2-4 days
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESA. CLASSIFICATION AND PHARMACOKINETICS Erythromycin and clarithromycin
Elimination of intact drug is rapid Biliary excretion
Erythromycin Hepatic metabolism and urinary excretion
Clarithromycin Half-life is 2-5 hours
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESB. ANTIBACTERIAL ACTIVITY Erythromycin
Campylobacter Chlamydia Mycoplasma Legionella Gram (+) cocci, and some gram (-) organisms
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESB. ANTIBACTERIAL ACTIVITY Erythromycin
Erythromycin stearate Erythromycin lactobionate Erythromycin estolate
Best absorbed oral preparation
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESB. ANTIBACTERIAL ACTIVITY Azithromycin and clarithromycin
Same spectra of activity but include greater activity
Chlamydia M. avium complex (MAV) Toxoplasma
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESB. ANTIBACTERIAL ACTIVITY Resistance in gram (+) organisms
Efflux pump mechanisms Production of methylase that adds methyl group
to the ribosomal binding site Resistance to enterobacteriaceae
Formation of drug-metabolizing esterases
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESB. ANTIBACTERIAL ACTIVITY Cross-resistance between individual macrolides
is complete Partial cross-resistance with other drugs that bind
to the same site occur in methylase-producing strains
Clindamycin and streptogramins
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESC. CLINICAL USES Erythromycin
M. pneumonia Corynebacterium C. jejuni C. trachomatis L. pneumophilia U. urealyticum B. pertussis
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESC. CLINICAL USES Erythromycin
Gram (+) cocci like pneumococci (not penicillin-resistant S. pneumoniae
[PRSP]) Beta-lactamase-producing staphylococci
(not methicillin –resistant S. aureus [MRSA] strains)
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESC. CLINICAL USES Azithromycin Similar spectrum of activity but more active
H. influenzae M. catarrhalis Neisseria
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESC. CLINICAL USES Azithromycin
Long half-life, single dose is effective Urogential infections caused by C. trachomatis
4-day course is effective for community-acquiredpneumonia (CAP)
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESC. CLINICAL USES Clarithromycin
Prophylaxis against and treatment of M. avium complex
Component for drug regimens for ulcers caused by H. pylori
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESD. TOXICITY GI irritation is common
Stimulation of motolin receptors Skin rashes Eosinophilia
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESD. TOXICITY Erythromycin estolate
Hypersensitivity-based acute cholestatic hepatitis
Rare in children Increased risk in pregnant patients
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESD. TOXICITY Erythromycin
Inhibits several forms of cytochrome P450 Increases the plasma levels
Anticoagulants Carbamazepine Cisapride Digoxin Theophylline
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
MACROLIDESD. TOXICITY Clarithromycin
Similar drug interactions of erythromycin can occur
Azithromycin Structure of lactone ring is slightly different Drug interactions are uncommon Does not inhibit hepatic cytochrome P450
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TELITHROMYCIN Ketolide Structurally related to macrolides Same MOA as erythromycin Similar spectrum of antimicrobial activity Some macrolide-resistant strains are susceptible
because it binds more tightly to ribosomes
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
TELITHROMYCIN Poor substrate for bacterial efflux pump that mediate
resistance CAP and other upper respiratory tract infections Given orally once daily Eliminated in the bile and urine Inhibitor of cytochrome CYP3A4 isozyme
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CLINDAMYCINA. CLASSIFICATION AND PHARMACOKINETICS Lincosamides Lincomycin and clindamycin
Inhibit bacterial protein synthesis Mechanism similar to macrolides but are not
chemically related
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CLINDAMYCINA. CLASSIFICATION AND PHARMACOKINETICS Resistance
Methylation of the binding site on 50S Enzymatic inactivation
Cross-resistance with macrolides is common
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CLINDAMYCINA. CLASSIFICATION AND PHARMACOKINETICS Orally absorbed Good tissue penetration Eliminated partly by metabolism and partly by
biliary and renal excretion
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CLINDAMYCINB. CLINICAL USE AND TOXICITY Clindamycin
Severe infections Anaerobes like bacteroides
Backup drug against gram (+) cocci Prophylaxis for endocarditis in valvular heart
disease who are allergic to penicillin Active against P. carinii and T. gondii
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
CLINDAMYCINB. CLINICAL USE AND TOXICITY Clindamycin
Toxicity GI irritation Skin rashes Neutropenia Hepatic dysfunction Superinfection such as C. difficile and
pseudomembranous colitis Treated by oral vancomycin
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
STREPTOGRAMINS Quinupristin-dalfopristin
Combination of 2 streptogramins Bactericidal Postantibiotic effect
Duration of bacterial activity is longer than the half-lives of the 2 compounds
Used for PRP, MRSA and vancomycin-resistant staphylococci (VRSA) and resistant E. faecium
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
LINEZOLID First of a new class of antibiotics Oxazolidinones Gram (+) cocci, including strains resistant to
beta-lactams and vancomycin Binds to a unique site on the 23S ribosomal
RNA of 50S No cross-resistance with other protein synthesis
inhibitors
CHLORAMPHENICOL, TETRACYCLINES, MACROLIDES, CLINDAMYCIN, STREPTOGRAMINS, & LINEZOLID
LINEZOLID Resistance
Rare Decreased affinity of the drug for its binding site
Available in oral and parenteral form Thrombocytopenia and neutropenia occur in
immunocompromised patients