Antibiotics in Oral and Maxillofacial Surgery

ANTIBIOTIC S IN ORAL & MAXILLOFACIAL SURGERY

PRESENTED BY: DR HANEEFMODERATED BY : DR SHIREEN FATIMA

CONTENTS

HISTORY & INTRODUCTION

CLASSIFICATION PRINCIPLES OF

ANTIBIOTIC THERAPY ANTIBIOTIC SIDE

EFFEECTS ANTIBIOTIC RESISTANCE ANTIBIOTIC FAILURES MISUSE OF ANTIBIOTICS ANTIBIOTIC

PROPHYLAXIS INDIVIDUAL DRUGS - Chemistry - Mechanisms of action - Spectrum - Sensitive organisms - Resistance - Adverse effects - Uses

SPECIAL CONDITIONS- Pregnancy

- Chronic renal failure- Hepatic failure- Diabetes mellitus- Head and neck infections

in immunocompromised state

NEWER ANTIBIOTICS ANTICANCER DRUGS SHOULD ANTIBIOTICS

BE USED? CONCLUSION REFERENCES

INTRODUCTIONANTIBIOTIC TERMINOLOGY

DEFINITION: SUBSTANCES DERIVED FROM MICROORGANISMS WHICH SUPPRESS THE GROWTH / KILL THE MICROORGANISMS AT A VERY LOW CONCENTRATIONOR

A CHEMICAL SUBSTANCE PRODUCED BY MICROORGANISMS HAVING THE PROPERTY OF INHIBITING THE GROWTH OF OR DESTROYING OTHER MICROORGANISMS IN HIGH DILUTION

CHEMOTHERAPY :TREATMENT OF SYSTEMIC INFECTIONS WITH SPECIFIC DRUGS THAT SELECTIVELY SUPPRESS THE INFECTING MICROORGANISM WITHOUT SIGNIFICANTLY AFFECTING THE HOST.

TERMINOLOGY Antimicrobial - This term refers to both antibiotics and

synthetic agents active against microbes. Microcidal - (Bacteriocidal. Vincidal, Fungicidal) The organism

is lysed or killed by direct damage on susceptible cell targets. Microstatic - (Bacteriostatic, Virostatic, Fungistatic)

The organism is reversibly inhibited at specific metabolic processes.

action and host defense mechanisms. Multiplication of the organism is inhibited.

Narrow Spectrum Antimicrobial - An antimicrobial that acts on a limited number of microbial species, e.g. Nitroimidiazole derivatives etc

Broad Spectrum Antimicrobial - An antimicrobial that acts on a wide range of species, e.g., erythromycin for Gram positive. Gram negative, Legionella, Mycoplasma, etc.

HISTORY (A) The period of emperical use South American Indians used

the bark of the cinchona tree to extract quinine to control malaria and mercury was known to cure syphilis in the late 1400's,‘mouldy curd’ by Chinese on boils, mercury by Paracelsus (16th century) for syphilis, Cinchona bark (17th century) for fevers.

(B) Ehrlich’s phase of dyes & organometallic compounds (1890-1935): methylene blue, tryptan red, etc.

He coined the term ‘Chemotherapy’

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HISTORY (C) The Modern Era of chemotherapy was ushered in by

Domagk in 1935 by demonstrating the therapeutic effect of prontosil , a sulfonamide dye in pyogenic infection.

Other pioneers in the field of antibiotics were Louis Pasteur,

Alexander Fleming, Chain Florey , Waksman.

All received Nobel prizes for their discoveries.

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CLASSIFICATION BASED ON TYPE OF ORGANISM THEY ACT

UPON:1. Antibacterial – penicillin amino glycosides erythromycin 2. Antifungal - griseofulvin amphotericin ketoconazole3. Antiviral- acyclovir amantidine zidovudine4. Antiprotozoal- metronidazole chloroquine

BASED ON MECHANISM OF ACTION: 1. Inhibit cell wall synthesis: penicillins cephalosporins cyclosporins2. Leakage from cell membrane: polypeptides-polymixin, bacitracin polyenes- amphotericin B ,nystatin3. Inhibits protein synthesis: tetracyclines, chloramphenicol, erythromycin, clindamycin.4. Causes misreading of m.RNA: aminoglycosides5. Inhibits DNA gyrase: fluoroquinolones6. Interfere with DNA function : rifampin, metronidazole.7. Interfere with DNA synthesis: acyclovir, idoxuridine.

CHEMICAL STRUCTURE Sulfonamides and related drugs :

○ Sulfones – Dapsone (DDS) ○ Para amino salicylic acid (PAS)

Diaminopyrimidines ○ Trimethoprim, pyrithamine

Quinolones ○ Nalidixic acid, Norfloxacin, Ciprofloxacin etc

- lactam antibiotics ○ Penicillins, cephalosporins, monobactams, carbapenems

Tetracyclines ○ Oxytetracycline, Doxycycline etc

Nitrobenenzene Derivative ○ Chloramphenicol

Aminoglycosides ○ Streptomycin Gentamycin, Neomycin etc

- Macrolide antibiotics ○ Erythromycin, Roxithromycin, Azithromycin etc

Polypeptide antibiotics ○ Polymyxin – B, colistin, Bacitracin, Tyrothricin etc

Glycopeptides ○ Vancomycin, Teicoplamin

Oxazolidinase ○ Linezolid

Nitrofuran derivatives ○ Nitrofurantoin, Furazolidine

Nitroimidazoles ○ Metronidazole, Tinidazole

Polyene antibiotics ○ Nystatin, Amphotericin – B, Hamycin

Azole derivatives ○ Miconazole, clotrimazole, ketoconazole, fluconazole

SPECTRUM OF ACTIVITY

Narrow spectrum Penicillin G, streptomycin and

erythromycin. Broad spectrum Tetracyclines, chloramphenicol. Extended spectrum Semi synthetic Penicillins, new

cephalosporins, aminoglycoside.

TYPE OF ORGANISMS AGAINST WHICH PRIMARILY ACTIVE : Antibacterial Penicillins, Aminoglycosides, erythromycin etc

Antifungal Griseofulvin, amphotericin B, ketoconazole etc Antiviral Idoxuridine, Acyclovir, Amantadine, Zidovudine etc

Antiprotozoal Chloroquine, pyrimethamine, metronidazole etc Antihelminthic Mebendazole, nicosamide, diethyl carbamazine etc

CLASSIFICATION(v) TYPE OF ACTION:

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Primarily Bacteriostatic Primarily Bactericidal

SulfonamidesTetracyclines

ChloramphenicolErythromycinEthambutol

Penicillins , Cephalosporins,Aminoglycosides,

Vancomycin, Ciprofloxacin, Isoniazid ,Rifampin, Cotrimoxazole,

SOURCE Fungi

Penicillin, Cephalosporin, Griseofulvin. Bacteria

Polymyxin B, Colistin, Bacitracin, Tyrothricin Aztreonam.

Actinomycetes Aminoglycosides, Tetracyclines, Chloramphenicol,

Macrolides, Polyenes.

PRINCIPLES OF ANTIBIOTIC THERAPY

PRINCIPLE 1: TO DETERMINE THE SEVERITY OF INFECTION

PRINCIPLE 2: TO EVALUATE STATE OF PATIENT’S HOST DEFENSE MECHANISMS

PRINCIPLE 3:TO DETERMINE WHETHER PATIENT SHOULD BE TREATED BY GENERAL DENTIST OR SPECIALIST

PRINCIPLE 4:TO TREAT INFECTION SURGICALLY

PRINCIPLE 5 :TO SUPPORT THE PATIENT MEDICALLY

PRINCIPLE 6 : CHOOSE AND PRESCRIBE APPROPRIATE ANTIBIOTIC

PRINCIPLE 7 : PROPER ANTIBIOTIC ADMINISTRATION

PRINCIPLE 8 :MONITORING THE PATIENT

DETERMINATION OF THE SEVERITY OF INFECTION

Complete history-Time of onset -Duration of infection -Rapidity of progress

Eliciting patient’s symptom

Physical examination

DIFFERENCES BETWEEN CELLULITIS AND ABSCESS

CHARACTERISTIC CELLULITIS ABSCESS

Duration Acute Chronic

Pain Severe and generalized Localized

Size Large Small

Localization Diffuse borders Well circumscribed

Palpation Doughy to indurated Fluctuant

Presence of pus No Yes

Bacteria Aerobic Anaerobic

2)TO EVALUATE STATE OF PATIENT’S HOST DEFENSE MECHANISMS Uncontrolled metabolic diseases e.g. – uremia, alcoholism, malnutrition, severe diabetes

(decreased function of leucocytes, decreased chemotaxis, decreased phagocytosis, decreased bacterial killing)

2- Immuno Suppressing diseasesInterfere with host defense mechanisme.g.- leukemias, lymphomas, malignant tumours

3- Immuno Supressing drugs e.g.- cancer chemotherapeutic drugs Immunosuppressive agents

3)TO DETERMINE WHETHER PATIENT SHOULD BE TREATED BY GENERAL DENTIST OR SPECIALIST

Criteria for referral to a specialist : 1.Rapid progressive infection 2.Difficulty in breathing 3.Difficulty in swallowing 4.Fascial space involvement 5.Elevated temperature(>101 degree F) 6.Severe jaw trismus(<10mm) 7.Toxic appearance

4)TO TREAT INFECTION SURGICALLY GOALS : 1.To remove the cause of infection 2.To provide drainage of accumulated pus and necrotic debris MODES : 1.Endodontic treatment 2.Extraction 3.Incision and drainage +extraction\ endodontic treatment Drainage of pus Reduction in tissue tension Improved local blood supply and increased

delivery of host defenses

5)TO SUPPORT THE PATIENT MEDICALLY

Odontogenic infection

Pain and swelling

No adequate fluid and nutritional intake

Depressed host defenses

Adequate analgesics and fluid intake

6)CHOOSE AND PRESCRIBE APPROPRIATE ANTIBIOTIC

PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC

Identification of causative organism Scientifically determined either in the laboratory, where

the organism can be isolated from pus, blood or tissue or Empirically based upon the knowledge of the

pathogens and clinical presentation of specific infection.


(I) IDENTIFICATION OF THE CAUSATIVE ORGANISM:-

Scientifically - laboratory Emperically – knowledge of the pathogenesis & clinical presentation. Initial emperical therapy instituted with a fair degree of reliability.

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Typical odontogenic infection is caused by a mixture of aerobic & anaerobic bacteria (70%)

Aerobic bacteria – 5% (gm positive cocci) Pure anaerobic bacteria – 25% (gm positive cocci – 30% & gm

negative rods – 50%) All are sensitive to penicillin & penicillin like drugs, but

Fusobacterium frequently resistant to erythromycin (apprx. 50%)

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Oral and Maxillofacial Surgery Clinics of NA :2003

TYPE OF INFECTION MICROORGANISMS

ODONTOGENIC CELLULITES/ABSCESS

STREPTOCOCCUS MILLERI GROUPPEPTOSTREPTOCOCCI PREVOTELLA AND PORPHYROMONASFUSOBACTERIA

RHINOSINUSITIS ACUTE STREPTOCOCCUS PNEUMONIAEHAEMOPHILUS INFLUENZAEHEAD AND NECK ANAEROBES

(PEPTOSTREPTOCOCCI, PREVOTELLA PORPHYROMONAS, FUSOBACTERIA)

GROUP A BETA-HEMOLYTIC STREPTOCOCCISTAPHYLOCOCCUS AUREUSMORAHELLA CATARRHALISVIRUSES

CHRONIC HEAD AND NECK ANAEROBES

FUNGAL ASPERGILLUSRHIZOPUS SP. (MUCOR)

NOSOCOMIAL(ESPECIALLY IF

INTUBATED)

ENTEROBACTERIACEAE (ESPECIALLY PSEUDOMONAS, ACINETOBACTER, ESCHERICHIA COLI)

S. AUREUSYEASTS (CANDIDA SPECIES)

Major pathogens of head and neck infections


Pathobiology of mixed odontogenic infection:-

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Entry of organisms (aerobic)

Effects underlying tissues

Cellulitis develops Condtion resolves on treatment

Hypoxic acidotic condition

Tissue destruction and abscess formation

(anaerobic)

Production of enzymes and toxins


CULTURES SHOULD BE PERFORMED:-

1. Pt. with an infection has compromised host defenses2. Received appropriate treatment for 3 days without

improvement3. Postoperative wound infection4. Recurrent infection5. Actinomycosis is suspected, or6. Osteomyelitis is present

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(II) DETERMINATION OF ANTIBIOTIC SENSITIVITY:-

Not responded to initial antibiotic therapy or a postoperative wound infection – causative agent identified & the antibiotic sensitivity determined.

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DISK DIFFUSION METHOD

RATIONALE : Antibiotics diffuse into the agar and inhibit the

growth of sensitive bacteria in a semicircular zone around the disc.

When the resistance to a given agent is present, the zone radius will be reduced or these will be no zone at all.

Advantages : Simple to perform Inexpensive Provides data within 18 to 24 hours Disadvantages : It is only semi quantitative and is not useful for

many flow growing or fastidious organisms. It has not been adequately standardized for

anaerobic bacteria.


The result of these studies provide the information needed to

prescribe the most appropriate antibiotic.

Penicillin is excellent for treatment of streptococcus infection & is good to excellent for the major anaerobes of

odontogenic infections.

Erythromycin - Streptococcus, Peptostreptococcus & Prevotella

but is ineffective against Fusobacterium.

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Clindamycin – streptococcus & major anaerobic groups.

Cephalexin – moderately active against streptococcus & is

good to excellent against anaerobes.

Metronidazole – no activity against streptococcus but has

excellent activity against anaerobes.

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(III) USE OF A SPECIFIC, NARROW SPECTRUM ANTIBIOTIC:-

Advantages - less chances of developing resistant organisms.E.g. streptococcus sensitive to penicillin , cephalosporin and

tetracycline. Minimizes the risk of super infections.E.g. moniliasis and gram negative pneumonias

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(IV) USE OF THE LEAST TOXIC ANTIBIOTIC:-

Equally effective but less toxic drugs have to be used.

E.g. bacteria causing odontogenic infection susceptible to both

penicillin and chloramphenicol.

More toxicity present with the latter drug.

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(V) PATIENT DRUG HISTORY:- Previous allergic reactions Previous toxic reactions Allergy rate to penicillin - 5 % Cross sensitivity Penicillins and cephalosporins. Toxic reactions - identify the drug and precise reaction Likely to happen again.

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(Pharmacologic factors in antibiotic selection)(VI) USE OF A BACTERICIDAL RATHER THAN A

BACTERIOSTATIC DRUG:-Advantages:

1. Less reliance on the host resistance

2. killing of the bacteria by the antibiotic itself

3. Faster results

4. Greater flexibility with dosage intervals.

Used especially when the host defenses are low.

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(VII) USE OF THE ANTIBIOTIC WITH A PROVEN H/O SUCCESS:-

Critical observation of the clinical effectiveness over a prolonged period -----assessment of Frequency of treatment success and failures Frequency of adverse reactionsFrequency of side effectsStandards for use

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(VIII) COST OF THE ANTIBIOTIC:-

Difficult to place a price tag on health. In some situations, more expensive antibiotic is the drug of

choice. In other situations, there may be a substantial difference in price

for drugs of equal efficacy. Surgeon should consider the cost of the antibiotic prescribed.

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(IX) ENCOURAGE PATIENT COMPLIANCE:- Dosage interval that encourages compliance

OD 80%BID 69%TID 59%

QID 35% Non-compliant start feeling better

3-5 days 50%>7 days 20%

Antibiotic that would have the highest compliance would be the drug given OD for 4 or 5 days.

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Indications for use of antibiotics Rapidly progressive swelling Diffuse swelling Compromised host defenses Involvement of facial spaces Severe pericoronitis Osteomyelitis

Use of antibiotics is not necessary Chronic well localized abscess

Minor vestibular abscess

Dry socket

Mild pericoronitis

INDICATIONS OF EMPIRICAL ANTIBIOTIC THERAPY :

The site and feature of the infection have been well defined.

The circumstances leading to the infection are well known.

Organisms that most commonly cause such infections.

EMPIRIC ANTIBIOTIC TREATMENT Early infection (first 3 days of symptoms and mildly

immunocompromised) Penicillin Clindamycin Cephalexin Late infection (After 3 days of symptoms or moderately to severely

immunocompomised) Clindamycin Revicillin and metranidazole. Ampicillin and sulbactam. Cephalosporin (first or second generation). -Mild, moderate and severe compromised based on CD4 / viral

loads, glycemic control, and the degree of alcoholic related disease.

7)PROPER ANTIBIOTIC ADMINISTRATION

Proper dose. Proper time interval. Proper route of administration. Combination antibiotic therapy.

It is indicated in few situations like in: Situations of life threatening situations of unknown cause. To increase the bactericidal effect of a specific organism. Prevention of the rapid emergence of resistant bacteria.

- Empiric therapy of certain odontogenic infections like when the infection progresses to the lateral and retropharyngeal spaces and caused by aerobes and anaerobes.

PRINCIPLES OF ANTIBIOTIC DOSING

GOAL : 1.To aid the body’s defenses to clear the

tissues of microbial pathogen by achieving antibiotic levels in the infected area to or greater than the MIC

ANTIBIOTIC DOSING VARIABLES PHARMACOKINETIC FACTORS Diffusion to the site of action

1.Tissue pH. 2.Lipid and water solubility 3.Plasma protein binding INOCULUM EFFECT- It is defined as a laboratory phenomenon

that results in significantly increased MIC required of an antibiotic. When the number of inoculated organisms increases. It generally occurs in case b-lactum antibiotics and b-lactamase producing bacteria

(review of infectious diseases vol.2 number.3 may- june 1989) SURFACE AREA TO VOLUME RATIO

Lipophilic antibiotics

Tetracyclines,macrolides,fluoroquinolones

Pass better through tissue barriers

Effective against intracellular pathogensDrug depot within macrophages

Hydrophilic antibiotics

Beta-lactams,vancomycin,aminoglycosides

Confined to ECF

Poor diffusion through capillaries

PLASMA PROTEIN BINDING

Limited plasma protein binding

Diffuse easily through capillary wallsand

other barriers

PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE

(I) PROPER DOSE:- Dose – 3 to 4 times the MIC

for e.g. penicillinase producing staphylococcus -

MIC 6 µg/ ml , plasma level - 18µg /ml Administration of doses above this level – increases the

likelihood of toxicity & is wasteful. Sub therapeutic levels - mask the infection ,recurrence.

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DRUG DOSE CALCULATION BASED ON BODY SURFACE AREA Individual dose = BSA[m2] x adult dose 1.7 BASED ON BODY WEIGHT

Individual dose = BW[kg] x average 70 adult dose

IN PEDIATRICS

YOUNG’S FORMULA :

CHILD DOSE = Age x adult dose Age + 12DILLING’S FORMULA :

CHILD DOSE = Age x adult dose 20

NEONATES AND INFANTS

Greater percentage of body weight compared with body water

Greater volume of distributionIncreased serum half lives

Reduced gastric emptying Reduced plasma protein binding

Reduced GFR

ELDERLY

Reduced host defenses Underlying illness Reduced total body water Lean body mass Reduced cardiac output Reduced gastric emptying time Decreased renal function

LOADING DOSE; This is a single or few quickly repeated doses given in the beginning to attain target concentration capacity.

MAINTAINANCE DOSE: This is the dose repeated at specific interval after attainment of target cycles per second

ANTIBIOTIC LOADING DOSES INDICATIONS : 1.The half-life of the antibiotic is longer

than 3-hours. 2. A delay of longer than 12-hours to

achieve therapeutic blood levels is unacceptable.

Because most acute orofacial infections begin and peak rapidly

DURATION OF ANTIBIOTIC DOSING

The ideal antibiotic duration is the shortest time that will prevent both clinical and microbiological relapse.

Clinical improvement of the patient Remission of infection.

MISCONCEPTIONS IN LONGER DURATION OF ANTIBIOTICS

Prolonged antibiotic therapy destroys resistant bacteria.

Prolonged antibiotic therapy is necessary to prevent rebound infections.

The dosage and duration of therapy can be extrapolated from one infection to another.

The prescriber knows how longer the infection will last.


(II) Proper time interval:- Established plasma t 1/2 – one half of the absorbed dose is

excreted. Usual dosage interval for therapeutic use of antibiotics - Four

times the half life.E.g. cefazolin t 1/2 - 2 hours.

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(III) Proper route of administration:-In some infections , only the parenteral route produces necessary serum level of antibiotic

For e.g. Penicillin V oral - 2 gm Plasma level - 4 µG/ mL

Oral route - variable absorption.

Serious well established infection - parenteral route

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(IV) Consistency in Route of Administration:-After initial response , immediate discontinuation of parenteral route - Recurrence

Maintenance of peak blood levels of antibiotic for an adequate period is important – max. tissue penetration & effective bactericidal action.

After the 5th day of parenteral administration, the blood levels achievable with oral administration are usually sufficient.

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(V) Combination Antibiotic therapy:- Life threatening sepsis of unknown cause Increased bactericidal effect against a specific µorg is desired.E.g. treatment of infections caused by enterococcus Prevention of rapid emergence of resistant bacteriaE.g. tuberculosis Empiric treatment of certain odontogenic infections E.g. Penicillin G & Metronidazole

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COMBINATION ANTIBIOTIC THERAPY

Combination therapy with two or more antibiotics is used in special cases:

Prevent the emergence of resistant strains

To treat emergency cases during the period when an etiological diagnosis is still in progress

To take advantage of antibiotic synergism

ADVANTAGES vs DISADVANTAGES Broad antibacterial

spectrum

Reduced dose for each agent.

Antibiotic synergism

Decreased adverse drug reactions

Greater likelihood of adverse reactions

Antibiotic antagonism

Increased financial costs

Greater microbial resistance

Resistance genes

Increased risk of superinfection

SYNERGISTIC ANTIBIOTIC COMBINATION

Cell wall inhibitors and aminoglycosides

Beta-lactams with beta-lactamase inhibitors

Beta-lactams that act on different PBPs

Sulfonamides and trimethoprim


Should be avoided when not specifically indicated.

Usual result – broad spectrum exposure that leads to depression of the normal host flora & inc opportunity for resistant bacteria to emerge.

For routine infections, the disadvantages of combination therapy outweigh the advantages.

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FACTORS INFLUENCING Minimal Inhibitory Concentration Post-antibiotic effects Microbial persistence and regrowth. Dosing and resistance Antibiotic loading dose Duration of antibiotic dosing Incision and Drainage Special conditions

MINIMAL INHIBITORY CONCENTRATION Is the lowest antibiotic concentration that prevents growth

of microorganism after an incubation period of 18 – 24 hours incubation period with a standard inoculum of 104 to 105 cfu/ml

MINIMAL BACTERICIDAL CONCENTRATION Is the lowest concentration of drug that causes the

complete destruction of the organisms or permits survival of less than 0.1% of the inoculum

ADVANTAGES IN DETERMINING MIC DETERMINES: 1.The ratio of the peak drug

concentration in the serum to the MIC 2.The duration of the time the serum

drug concentration exceeds the MIC 3.The ratio of the 24-hour area under

the curve [AUC] to the MIC The AUC is the measure of

the drug exposure to the bacteria over time

DISADVANTAGES WITH MIC Is only a point in time and tells nothing about the

true antibiotic activity at the locus of infection The concentration of organisms at the site of

infection is 108-1010 cfu/ml – greater than that used to determine the MIC in the laboratory.

Exponential growth in vitro Differing variables- temperature, inoculum Size,

pH and growth period.

RULE OF THUMB

The concentration of the antibiotic in the blood should exceed the MIC by a factor of 2-8 times to offset the tissue barriers that restrict access to the infected site.

CONCENTRATION DEPENDENT Vs

TIME DEPENDENT ANTIBIOTICS

CONCENTRATION DEPENDENT

TIME DEPENDENT ANTIBIOTICS

1. Aminoglycosides, metronidazole, fluroquinolones

2. Bactericidal activity depends on the drug concentration

1. Beta-lactams and vancomycin

2. Long time of exposure of the organisms

3. Better the bactericidal concentration

4. Require organisms in the process of cell division

POSTANTIBIOTIC EFFECTS Is the persistent supression of microbial growth

after short time exposure to an antimicrobial agent.

MECHANISM : Is the time necessary to recover from

sublethal structural and metabolic alterations that prevents resumption of bacterial regrowth.

FACTORS INFLUENCING PAE

The particular organism Inoculum size Growth medium Organism growth phase Mechanism of action of antibiotic Duration of exposure to the drug

MICROBIAL PERSISTENCE AND REGROWTH.

The subpopulation of organisms that is not inhibited or killed during a given dose interval which can then reestablish themselves and continue growth.

FACTORS DETERMINING : 1.Initial inoculum size 2.Bactericidal activity 3.Organism MIC 4.Post-antibiotic effects 5.Antibiotic pharmacokinetics 6.Doubling time of the organism.

8)MONITORING THE PATIENT1)Response to treatment. Reasons for treatment failure:-Inadequate surgical treatment.-Depressed host defences.-Presence of foreign body.-Antibiotic problems – Drugs not reaching infection.

Dose not adequate Wrong bacterial

diagnosis.Wrong antibiotic.

2)Development of adverse reactions:3)Superinfection and recurrent infection:

ANTIBIOTIC SIDE EFFECTS Side effects are unwanted but often unavoidable

pharmacodynamic effects that occur at therapeutic doses.

1) HAEMATOLOGIC EFFECTS a) Leucopenia and thrombocytopenia: Beta lactams sulfonamides(Cotrimazole) b) Anaemia: Beta lactam- Autoimmune anaemia Cotrimazole- Folate deficiency- Megaloblastic anaemia Chloramphenicol- Aplastic anaemia. c) Platelet dysfunction: Anti pseudomonal penicillins- Impaired platelet aggregation. d) Clinical bleeding: Moxalactam- Interferes with vit.K depended clotting factor synthesis. Trovafloxacin- Increases prothrombin time.

2) HYPERSENSITIVITY EFFECTS Drug fever: 10-15% of unexplained fever in hospitalized patients. Beta lactams, Sufonamides.

Drug rashes: Itching, urticaria, maculo popular rashes. Beta lactams, sulfonamides.

Anaphylactic reactions: Beta lactams, rare in Sulfonamides.

Serum sickness: Develops 2 weeks after exposure- Beta lactams.

Photosensitivity reactions: Tetracycline, Sparfloxacin Rare with Doxycyclin, minocycline

Drug induced Systemic Lupus Erythematosus(SLE): Minocyclin, Isoniazide, Nitrofurantoin, Griseiofulvin.

3) NEUROLOGIC EFFECTS

a) Encephalopathy: Trovafloxacin- Mental confusion

Clarithromycin b) Seizures: Ciprofloxocin, Imipenem,

Trovafloxacin. It depends on seizure threshold of patient. c) Neuromuscular blockade: Aminoglycosides d) Peripheral neuropathy: Isoniazide, Griseiofulvin e) Muscular tremors and myalgias: Trovafloxacin f) Ototoxicity: Aminoglycisides, Parenteral

Erythromycin g) Blindness: Ethambutol, Chloroquine.

4) PULMONARY EFFECTS a) Acute pulmonary reactions: Rifampicin- Flu like illness. Nitrofurantoin: Varying degrees of respiratory Insufficiency, Pleural effusion.

b) Chronic pulmonary reaction: Nitrofurantoin- Pulmonary fibrosis.

5) CARDIAC EFFECTS

a) Ventricular arrhythmias: Erythromycin

b) Hypotension: Trovafloxacin, Amphotericin-B

6) GASTROINTESTINAL EFFECTS

a)Nausea and vomiting

Clarithromycin,Amoxicillin/Clavulanate,Azithromycin,

Doxicycline,Minocycline.b) Non-clostridium difficile diarrhea: Macrolides,Ampicillin, Trovafloxacin c)Cl. Difficile diarrhoea Beta lactums, Quinolonesd)Anti pancreatitis Trovafloxacin.

7)HEPATIC SIDE EFFECTSa) drug induced hepatitis -Isoniazide- elevates serum transaminas, Trovafloxacin,Oxacillinb) Cholestasis-Erythromycin,Nitrofurantoinc) Hepatic necrosis-PAS, Ketoconazole or Trovafloxacin

8)NEPHROTOXIC SIDE EFFECTSa) Nephrotoxicity Aminoglycosides-Tubular toxicity. Tetracyclines, Polymyxin –Bb) Interstitial nephritis Beta lactamase therapy.

ANTIBIOTIC RESISTANCE The organisms continue to multiply even in the

presence of antibiotic. Resistance to an antimicrobial can arise (1) Mutation in the gene that

determines sensitivity/resistance to the agent or (2) Acquisition of

extrachromosomal DNA (plasmid) carrying a resistance gene.

(3) Bacteriophages. (4) Mosaic genes Mutation: random, undirected, heritable variation caused by an

alteration in the nucleotide sequence at some point of the DNA of the cell

CROSS RESISTANCE Single mechanisms confers resistance to

multiple antimicrobial agents MULTIPLE RESISTANCE Multiple mechanisms Cross resistance - closely related antimicrobial

agents Multiple resistance - unrelated antimicrobial

agents.

ANTIBIOTIC RESISTANCE MECHANISMS

1.ENZYMATIC ANTIBIOTIC INACTIVATION a.Beta-lactams - beta lactamases b.Aminoglycosides - aminoglycosides modifying enzymes c.Chloramphenicol - acetyl transferases

2.MODIFICATION \ PROTECTION OF TARGET SITE a.Beta-lactams-altered PBPs b.Fluoroquinolones:altered DNA gyrases c.Rifampin:altered RNA polymerase d.Sulfonamides: altered dihydropteroate synthase

3.LIMITING ACCESS OF ANTIBIOTICBeta-lactams and fluoroquinolones Altered outer membrane porins

4.ACTIVE ANTIBIOTIC EFFLUX

5.FAILURE TO ACTIVATE ANTIBIOTIC Metronidazole - flavodoxin production

6.USE OF ALTERNATE GROWTH REQUIREMENTS

7.OVERPRODUCTION OF TARGET SITES

a.Sulfonamides:overproduction of PABA b.Entericbacilli:overproduction of

beta- lactamases

ANTIBIOTIC FAILURESCommon reasons for antibiotic failure:

1.Failure to surgically eradicate - source of infection

2.Too low - blood antibiotic concentration

3.Inability to penetrate the site of infection

4.Impaired host defenses

5.Patient failure to take the antibiotic

6.Inappropriate choice of antibiotic

7.Limited vascularity or blood flow

8.Decreased tissue ph or oxygen tension

9.Antibiotic resistance

10.Delay or incorrect diagnosis

11.Antibiotic antagonism

MISUSE OF ANTIBIOTICS

1) Treatment of untreatable infections 2) Therapy of fever of unknown origin 3) Improper dosage 4) Inappropriate reliance on

chemotherapy alone 5) Lack of adequate bacteriological

information

DEVELOPMENT OF DRUG RESISTANCE

Refers to unresponsiveness of a microorganism to an AMA

Natural Resistance

Acquired Resistance

.

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Single step mutationE.g. Enterococci to Streptomycin, E.coli &

Staphylococci to rifampin Multistep mutationE.g. resistance to erythromycin, tetracyclines &

chloramphenicol by many organisms.

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Gene Transfer:- from organism to another can occur by,

(i) Conjugation:-

E.g. Chloramphenicol – typhoid bacilli, Streptomycin – E.coli, Penicillin – Haemophilus &

Gonococci(ii) Transduction:-

E.g. Penicillin, Erythromycin & Chloramphenicol

(iii) Transformation:-

E.g. pneumococcal resistance to Penicillin G 94

PRINCIPLES OF PROPHYLACTIC ANTIBIOTICS

It is the use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications.

ADVANTAGES:1.Prevention of infection.2.Decrease patient morbidity and mortality.3.Decrease hospital stay.4.Decreased medical cost.5.Decreased total antibiotic usage.6.Decrease numbers of resistant bacteria – because of

short term course.

DISADVANTAGES No reduction of infection.

Development of increased number of resistant bacteria.

Delay in onset of infection.

Adverse effect on surgical technique

THE PRINCIPLES FOR PROPHYLACTIC ANTIBIOTICS

Increased risk of significant bacterial contamination and a high incidence of infection.

Organism must be known. Antibiotic susceptibility must be known. To be effective and to minimize adverse effects the

antibiotic must be in the tissue at the time of contamination (operation) and it must be continued for not more than 4 hours after cessation of contamination.

Four times the MIC of the causative organisms. Timing the antibiotic correctly. Shortest effective antibiotic exposure.

PRINCIPLE 1: PROCEDURE SHOULD HAVE A SIGNIFICANT RISK OF INFECTION

1.Bacterial inoculum of sufficient size

2.Extensive and prolonged surgery

3.Insertion or presence of foreign body

4.Depressed host resistance

Type I. Clean wounds (no opening of mucosa in the oral cavity): Confirmed infection rate of 1 to 4%. Antibiotic prophylaxis not required.

Type II. Clean-contaminated wounds (opening of mucosa in the oral cavity, insertion of dental implants or intervention on inflammatory pathology):

Confirmed infection rate of 5 to 15%. These require antibiotic prophylaxis with drugs covering Gram positive and anaerobic micro-organisms.

Type III. Contaminated wounds (oncological pathology in which there is simultaneous action on the oral cavity and the neck): Confirmed infection rate of 16 to 25%. Antibiotic prophylaxis must be carried out to cover Gram negative organisms whose coverage in clean and cleancontaminated surgeries is disputed.

Type IV. Dirty and infected wounds. Confirmed infection rate of above 26%. These always need adequate antibiotic treatment.

CLASSIFICATION OF SURGICAL WOUNDS

PRINCIPLE 2: TO CHOOSE CORRECT ANTIBIOTIC

1.Effective against the most likely organism

2.Narrow spectrum antibiotic

3.Least toxic antibiotic

4.Bactericidal antibiotic

PRINCIPLE 3: ANTIBIOTIC PLASMA LEVEL MUST BE HIGH

To ensure diffusion of antibiotic into all fluid and tissue components

USUAL RECCOMENDED DOSE: Two times

the usual therapeutic dose

PRINCIPLE 4: TO TIME ANTIBIOTIC ADMINISTRATION CORRECTLY

Antibiotic must be administered before the surgery begins

Prolonged surgery

Additional antibiotic is required

Intraoperative dose intervals should be one half the usual therapeutic dose interval

PRINCIPLE 5: USE OF SHORTEST EFFECTIVE ANTIBIOTIC EXPOSURE

Continued antibiotic administration - no benefit once the surgical procedure is complete

Hence the final dose of the antibiotic - after surgical operation

Procedure lasts for Short procedure more than two hours

2nd dose of antibiotic is Single preop dose is required adequate

ANTIBIOTIC PROPHYLAXIS AGAINST INFECTIVE ENDOCARDITIS GOALS : 1.To reduce the intensity of bacteremia.

2.Assist the RES in killing the bacteria.

3.Decrease the bacterial adherence to the damaged heart valves and vegetations.

CONDITIONS CONSIDERD FOR ANTIBIOTIC PROPHYLAXIS

Antibiotic prophylaxis recommended : High risk condition 1.Prosthetic cardiac valves 2.Bioprosthetic valves 3.Previous bacterial endocarditis 4.Complex congenital CHD Moderate risk condition 1.Acquired valvular dysfunction 2.Hypertrophic cardiomyopathy 3.Other congenital cardiac malformation

ANTIBIOTIC PROPHYLAXIS NOT RECOMMENDED LOW RISK CONDITION: 1.Isolated atrial septal defect 2.Previous coronary artery bypass

graft surgery. 3.Mitral valve prolapse without

valvular regurgitation 4.Cardiac pacemakers and

defibrillators 5.Previous rheumatic fever without

valvular regurgitation

AHA RECOMMENDATIONS PROPHYLAXIS RECOMMENDED : 1.Extractions 2.Periodontal surgery 3.Implants placement 4.Endodontic surgery 5.Subgingival antibiotic fiber strips 6.Intraligamentary LA injections. NOT RECOMMENDED : 1.Restorative dentistry 2.LA injections 3.Intracanal endodontic treatment 4.post-op suture removal 5.Oral radiographs

ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS:

Penicillins. Cephalosporins. Erythromycins. Clindamycin and Lincomycin. Metronidazole. Aminoglycosides. Fluoro quinolones – ciprofloxacin. Sulfonamides and trimethoprim

PENICILLINS

Discovered in 1929, it was first antibiotic drug to be used.

The drug of choice for the initial empirical management of odontogenic infections remains penicillin

Bactericidal

Narrow but appropriate spectrum

Little or no toxicity

CLASSIFICATION OF PENICILLIN I) Natural penicillins :

Penicillin G (Benzyl penicillin)

II) Acid resistant penicillins : Phenoxymethyl penicillin (penicillin V)

III) Penicillinase – resistant penicillins : Acid labile : Methicillin, nafillin, cloxacillin, dicloxacillin

IV) Penicillins effective against gram +ve and some gram –ve organisms : Ampicillin

V) Extended spectrum penicillins : Carboxypenicillins : Carbenicillin, tiocillin

PENICILLIN-G ( Benzyl Penicillin )-Narrow spectrum activity Spectrum of activity- Streptococci except enterococci,

Staph. aureus, N. gonorrhoea, N. meningitides, Anthracis, C.diphtheriae, Clostridia, Listeria.

PHARMACOKINETICS: PnG is acid liable destroyed by gastric

acid. -Absorption of sodium PnG from i.m. site is rapid and

complete. -Distributed extracellularly, penetration into serous cavity and

CSF is poor. -Plasma T1/2 is 30 min. -Extreted through kidneys by glomerular filtration.

PREPARATION AND DOSE: 1) Sod. PnG or Crystallin penicillin injection: 0.5-5 MU i.m. 6-12 hrly

Repository PnG injections: These are insoluble salts must be given deep i.m. never given i.v. Drug is released slowly from the injection site.

Procaine PnG: 0.5-1MU i.m.12hrly

Fortified Procaine PnG : Contains 3lakhU

Procaine PnG and 1lakhU Sod. PnG

Benzathine PnG : 0.6-2.4MU i.m. every 2-4 weeks. It releases drug very slowly and effective for prophylactic purposes.

AMPICILLIN Semi synthetic penicillin belongs to aminopenicillins. Spectrum: Active against all organisms sensitive to PnG, H.Influenza, E.Coli, Proteus, Salmonella, Shigella,

Strepto. Viridans, Enterococci, Pseudomonas, Klebsiella.

Kinetics : Not degraded by gastric acid. Oral absorption is incomplete but adequate. Food interferes with absorption. Plasma T1/2 is 1 hr, excreted through kidneys. Dose: 0.5-2g oral /i.m. /i.v. every 6th hrly. Children 25-50mg /kg /day.

Uses: Urinary tract infections, Respiratory tract infections, Meningitis,

Gonorrhoea, Typhoid fever, Bacillary dysentery, Cholecystitis, SABE.

Adverse effects: Diarrhea is frequent after oral administration, rashes Avoided in patients with a H/O hypersensitivity to PnG.

AMOXICILLIN It is a close congener of Ampicillin, similar to it except - Oral absorption is better food does not interferes - Incidence of diarrhea is less. - Less active against Shigella, H.Influenza. Dose: 0.25-1g orally /i.m /i.v. TDS.

BROAD SPECTRUM EFFECT WITH CLAVULANIC ACID

Clavulanic acid- streptomycet clavuligerous-inhibiting β lactamase enzymes

Broaden antibacterial spectrum of amoxicillins

SULBACTAMSemisnythetic betalactamase inhibitorRelated chemically in activity to clavulanic acid Progressive inhibitor ,highly active against betalactamase2-3 times < potentOral absorption- inconsistent,preferably im/ivSulbactam+ ampicillin=DicapenSULBACIN, AMPITUM 1g+ 0.5g per vial im/iv 6-8hourly1g+500mg tab

ADVERSE EFFECTS : a) Local irritancy and direct toxicity

b)Jarisch-Herxheimer reaction

c) Hypersensitivity or drug allergy(1-10%)Defn: An allergic drug reaction is defined as any noxious, unintended, and undesired

effect of a drug that occurs at doses used in humans for prevention, diagnosis, or treatment.

2types predictable unpredictable PENICILLIN ALLERGY SKIN TESTING Reagents: Concentration-Penicilloate 0.01 mol/L-Penilloate 0.01 mol/L-Penicillin G 10,000U/ml-Ampicillin/Amoxicillin 1-20mg/ml

PROCEDURE:1) Epcutaneous or (scratch or prick)2) Intradermal test

DESENSITIZATION IN PENCILLIN ALLERGIC PATIENTS

Administration of a penicillin to a allergic patient, who requires penicillin for clearly defined medical reasons.

Ex; Endocarditis, meningitis. -Done in Intensive care setting… -Penicillin doses of 1,5,10,100 and 1000U

administered intradermally ,60 mints interval b/n doses.

-well tolerated- 10000U-50,000U given s.c.

Therapeutic Uses : Streptococcal infections Pneumococcal infections Meningococcal infections Staphylococcal infections Gonorrhoea Syphilis Diphtheria Tetanus and gas gangrene Antibiotic prophylaxis

CEPHALOSPORINS These are a group of semisynthetic

antibiotics derived from "cephalosporin – C" obtained from a fungus cephalosporium.

They are chemically related to penicillins, the nucleus consists of a -lactam ring fused to a dihydrothiazine ring.

CEPHALOSPORINS1ST GENERATION CEPHALOSPORINS Good against methicillin sensitive S. aureus,

streptococci and many Enterobacteriaceae. Members include: Cephalexin (Keflex), Cefazolin

(Ancef), Cephapirin (Cefadyl) and Cephalothin (Keflin) Cefadroxil.

2ND GENERATION CEPHALOSPORINS More stable to Gram negative b-lactamase and less

active against S. aureus. Members include: Cefuroxime (Ceftin [oral] and

Zinocef), Cefotetan (Cefotan), and Cefoxitin (Mefoxin).

3RD GENERATION CEPHALOSPORINS Broader activity against Gram negatives. Members include: Cefdinir (Omnicef),

Cefoperazone (Cefobid), Ceftazidime (Fortaz), and Ceftriaxone (Rocephin), and Cefotaxime (Claforan).

4TH GENERATION CEPHALOSPORINS More resistant to destruction by chromosomal b-

lactamases, but not completely resistant to the b-lactamases of Serratia, Enterobacter and Pseudomonas.

Cefepime (Maxipime).

Adverse effects : Pain Diarrhoea Hypersensitivity Nephrotoxicity Neutropenia Thrombocytopenia

USES : As alternatives to PnG in patients developing rashes or other allergic

reactions with PnG.

Respiratory, urinary and soft tissue infections caused by gram negative organisms.

Penicillinase producing staphylococcal infection.

Septicaermias caused by gram negative organisms : an aminoglycotide may be combined with a cephalosporin.

Surgical prophylaxis; surgical prosthesis such as artificial heart valves,

artificial joints etc. The first generation drugs are used.

Meningitis caused by H.influenzae, enterobacteriaceae. Gonorrhoea caused by penicillinase producing organisms. Typhoid : as alternative to fluoroquinolones (specially in children) Mixed aerobic – anaerobic infections seen in cancer patients those

undergoing colorectal surgery, obstetric complications. Prophylaxis and treatment of infections in neutropenic patients.

MACROLIDES (ERYTHROMYCIN), LONG ACTING MACROLIDES (AZITHROMYCIN), LINCOSAMIDES (CLINDAMYCIN) AND STREPTOGRAMINS (SYNERCID)

Bind to the 50s ribosomal subunit. Block chain elongation. Bacteriocidal or bacteriostatic depending upon

the organism.

ERYTHROMYCIN

USES Gram positive organisms.

Used to treat Legionella, Mycoplasma, syphilis, diphtheria carriers and pertussis.

Safe in pregnancy.

SIDE EFFECTS Erythromycin estolate - cholestatic hepatitis (1/1000). Ototoxic in high doses.

CLARITHROMYCIN

A.Uses Spectrum is similar erythromycin and respiratory Gram-negative pathogens Clarithromycin can be used - H. pylori and atypical mycobacteria infections.

B.Side Effects Teratogenic. Ototoxic in high doses.

CLINDAMYCIN

A.USES Used against Gram positive cocci and

anaerobes, both Gram-positive and Gram-negative rods.

B.SIDE EFFECTS Significant risk of pseudo-

membranous colitis due to the overgrowth of C. difficile.

AMINOGLYCOSIDES MECHANISM : Works by binding to a specific protein,

S12, on the 30s ribosomal subunit. Blocks normal activation of the initiation

complex. At low concentrations - the mRNA is misread

and the wrong amino acid is inserted. At higher concentrations - inhibit translation.

METABOLISM

Excreted by glomerular filtration.

Aminoglycosides have a low toxic to therapeutic

ratio. Blood levels need to be monitored to insure safety and efficacy.

If the GFR falls below 70mL/min, the daily dose must be reduced to prevent toxicity.

SIDE EFFECTS

Ototoxicity

Nephrotoxicity

Very high concentrations - neuromuscular blockade.

GENTAMICIN It is effective against gram positive and negative bacteria including

penicillinase resistant staphylococci.

Gentamicin and ampicillin should be administered separately because gentamicin gets destroyed.

It is indicated in severe anaerobic infections.

Dose – Adult – 3-7mg/kg/day in 2-3 divided dose. Child – 1-3mg/kg/day in 2-3 divided dose.

Toxicity – It causes ototoxicity (vestibular and cochlear). If serum concentrations exceeds 10mg/ml transient tinnitus may occur.

When used over a weak, nephrotoxicity occurs. Allergic reactions – not recommended in lactating mothers.

QUINOLONES CLASSIFICATION

First generation: Cinoxacin, Oxalinic acid, Nalidixic acid.

Second generation: Ciprofloxacin, Ofloxacin, Norfloxacin, Levofloxacin

Third generation: Gatifloxacin,

Sparfloxacin, Tosulfioxacin Fourth generation: Gemifloxacin, Moxifloxcin, Torvafloxacin.

QUINOLONES

Mechanism Interfere with the activity of DNA gyrase. Prevent winding of the DNA helix into the supercoiled form. Actions are bacteriocidal.

THERAPEUTIC USES Used against Enterobacteriaceae. Ciprofloxacin most active against Pseudomonas. Fluoroquinolones used for UTIs Pneumonia Atypical pneumonia and Bacterial gastroenteritis.

SIDE EFFECTS

High drug levels are neurotoxic. Prolonged use leads to tendon damage (rupture of

Achilles tendon). Not approved for children causes cartilage

damage. Safety in pregnancy is not established

METRONIDAZOLE

Belongs to Nitroimidazole group. Mechanism-In a reducing environment, metronidazole is

reduced to a substance - inhibits bacterial DNA synthesis.

-Its action is broadspectrum bacteriocidal-Its use is limited to anaerobic organisms. * Plasma t1/2 is 8hrs.

SIDE EFFECTS

Anorexia nausea and abdominal cramps. Produces metallic taste in the mouth. Peripheral neuropathy, seizures and ataxia have

been seen with prolonged use. Thromboflebitis of injected vein occurs if the

solution is not well diluted.

CONTRAINDICATIONS-Neurological disease.-Blood dyscrasias.-First trimister of pregnancy.-Chronic alcoholism.

Preparations: Tab Metrogyl 200mg 400mg 200mg/5ml susp 500mg/100ml i.v. infustion

USES Amoebiasis Giardiasis Trichomonas vaginitis Anaerobic bacterial infections Pseudomembranous enterocolitis Ulcerative gingivitis, trench mouth Helicobacter pylori gastritis/peptic ulcer

SULFONAMIDES AND TRIMETHOPRIM:

These are bacteriostatic agents. inactivated by presence of pus. They act by inhibition of bacterial synthesis of

folic acid from para amino benzoic acid (PABA).

The concentration of sulfonamides in the urine is greater than in blood this leads to formation of crystals of sulfonamides termed as crystalluria and leads to renal damage.

Toxic effects:

Allergic reactions Prolonged therapy can lead to macrocytic

anemia Also cause kernicterus by displacing

bilirubin from plasma albumin in babies during intrauterine life. They may also cause foetal malformation.

Sulfadizine: It penetrates blood brains barrier. It is commonly used in traumatic meningitis.

COTRIMOXAZOLE (SULFAMETHOXAZOLE AND TRIMETHOPRIM) This agent inhibits the conversion of folic acid to

folinic acid which is important for bacterial synthesis of DNA and RNA.

It is active against strep pyogens and most staphylococci and haemophili.

It is indicated in acute exacerbations in post irradiation osteomyelitis secondary to osteoradionecrosis. It is also used in mixed actinomycotic infections along with penicillin.

Dose 80 mg of Trimethoprim + 400 mg of sulfamethoxazole 2 tablets 12 hourly Child : 20 mg + 100 mg

USES : Cotrimoxazole is widely used Urinary tract infections Respiratory tract infections Typhoid Bacterial diarrhoeas and dysentery Chancroid Granuloma inguinale It is an effeictive alternative to penicillin for protecting

agranulocytosis patients and treating respiratory and other infections in them.

Pneumocystitis carinii.

TOPICAL ANTIBIOTICS

These are the antibiotics used for external application of drugs to the surface for local action.

POLYPEPTIDE ANTIBIOTICS Low molecular weight cationic drugs. Powerful bactericidal Toxic when used systemically. They are: Polymyxin-B, Colstin, Bacitran, Tyrothricin.

POLYMYXIN-B & COLISTIN Active against g-ve bacteria. They have a detergent like action on cell membrane causing leak in

cell constituents. No cross resistance with other drugs. Adverse effects: No systemic absorption after oral or topical

administration. Given orally causes G.I.T. disturbances. Systemic effects are flushing, paraesthesia, renal and CNS

disturbance.

Uses: 1. Topically used in combination with other anti microbials for skin infections, burns, otitis externa, conjunctivitis, corneal ulcers.

2. Orally for g-ve bacillary dysentery, diarrhea in children and infants.

Preparation and dose: 1. Neosporin powder: 5000u polymyxin with neomycin sulphate 3400u and bacitracin 400u per g.

Neosporin eye drops. Neosporin-H ear drops. BACITRACIN Discovered from Bacillus Subtilis. Active against g+ve organisms like Neisseria, H.Influenza,

Staph, Strepto, Clostridium, Corynebacterium. Not absorbed orally and does not penetrate the intact skin. Commonly combined with Neomycin and Polymyxin-B.

NEOMYCIN It is an aminoglyciside, obtained from Steptomyces Fradiaea.Binds to ribosomal 30S subunit to inactivate DNA polymerase cause

misreading of genetic code.

Spectrum: Active against g+ve and g-ve bacteria less active against Pseudomonas, Strepto. Pyogens. It is not used systemically because of nephro and ototoxicity. No systemic absorption from topical and oral administration.

Uses: a) Topical: Combined with Polymyxin-B & Bacitracin for infected wound, ulcers, burns, external ear infection, conjunctivitis.

Oral: -For preparation of bowel before surgery to decrease post operative infection. In hepatic coma to reduce nitrogen producing bacteria in G.I.T.

FOUR CATEGORIES BASED ON HOW SAFE OR RISKY IT IS

TO USE ANTIBIOTICS DURING PREGNANCY. Category A – No evidence of foetal harm.

Eg : Nystatin

Category B – No known association with birth defects Eg : Amoxicillin, Augmentin, Metronidazole

Category C – Information only from animal studies

Eg : Bactrim, isoniazid, rifampin

Category D – Clear - cut problems Eg : Tetracyclines, minocycline, sulfa drugs.

SPECIAL CONDITIONS-PREGNANCY

DRUG ADMINISTRATION DURING PREGNANCY AND BREAST FEEDING : Drug Use during

pregnancyRisk Use during

Breast feedingAntibiotics

Pencillins YES - YES

Erythromycin YES - Avoid estolate form

- YES

Cephalosporins YES - YES

Tetracylines AVOID Tooth discoloration inhibits bone formation

Avoid

Metronidazole YES - YES

Clindamycin YES - YES

RENAL FAILURE

Concentration-dependent antibiotics

Dosage interval should be increased

Time-dependent antibiotics

Dose is decreased

ANTIMICROBIALS NEED DOSE REDUCTION IN RENAL FAILURE

- Aminoglycosides - Cotrimoxazole - Cephalexin- Carbenicillin - Ethambutol - Cefotaxime - Vancomycin - Norfloxacin - Amphotenicin –B

- Metronidazole

DRUGS TO BE AVOIDED IN CHRONIC RENAL FAILURE :

Cephalothin Cephaloridine Talampicillin Tetracycline (except doxycline).

LIVER ATTENTION IN LIVER DISEASE : Antimicrobials to be avoided or used at lower dose in

liver disease are : Drugs to be avoided Dose reduction needed Erythromycin estolate Chloramphenicol

Pyrazinamide Metronidazole Talampicillin Clindamycin Tetracycline Isoniazid Nalidixic acid Rifampin Pefloxacin

The biliary concentration of ampicillin may be significantly reduced in patients with hepatic disease, rendering the antibiotic less effective.

THE DIABETIC PATIENT Antibiotic prophylaxis. Amoxicillin is better choice. Uncontrolled diabetes. PRECAUTION;Gatifloxacilin- causes both

hypoglycemia and hyperglycemia. Compared with macrolides- Gatifloxacilin 4.3 times higher risk hypoglycemia 16.7times higher risk hyperglycemia

MANAGEMENT OF HEAD AND NECK INFECTIONS IN THE IMMUNOCOMPROMISED PATIENT :

The immunocompromised host has a potential risk for severe head and neck infections that usually require aggressive antimicrobial therapy and prolonged hospitalization.

Management steps Airway monitoring and possible surgical airway

establishment. Comprehensive history and physical examination. Obtaining appropriate laboratory and imaging studies. Empiric antimicrobial therapy. Surgical debridement and irrigation, as needed. Culture and antibiotic sensitivity testing of infectious

organisms to appropriately adjust antibiotic therapy. Close follow-up to monitor for resolution and

recurrence.

NEWER ANTIBIOTICS 1. MEROPENEN It is a beta-lactam, belongs to the subgroup of

carbapenem. Ultra broad spectrum injectable antibiotic. Inhibits bacterial cell wall synthesis. Action against gram positive and gram negative

bacteria and some anaerobic bacteria. Administered intravenously.

CLINICAL USES Cystic fibrosis Infections in immunocompromised patients. Intra abdominal infections. Urinary tract infections. Septicaemia. Skin infections

ADVERSE EFFECTS : Diarrhoea, Nausea, Vomiting, headache, rash, thrombophlebitis.

2. CEFEPIME Fourth generation cephalosporin. Extended spectrum of activity against gram +ve and gram –ve

microbes compared to third generation cephalosporins. Administrated intramuscularly or intravenously dose –

1 gm to 2 gm every 12 hourly. PHARMACOKINETICS : Peak plasma concentration after i.m. administration is 1.0 to

1.6 hour. It is distributed throughout the body tissues and fluids. Primarily excreted unchanged in urine.

USES Lower respiratory tact infections. Urinary tract infections. Skin and skin structure infections. Sepsis and bacteremia Febrile neutropenia Meningitis.

ADVERSE EFFECTS : Headache, nausea, vomiting, rash, diarrhoea,

dizziness.

3. QUINUPRISTIN / DALFOPRISITIN (SYNERCID)

Synercid is the brand name of combination of quinupristin and dalfopristin antibiotics.

These are semisynthetic pistinamycin derivatives. Active against methicillius sensitive staphylococcus aureus,

group A streptococci, Enterococcus faecium.

500 mg strength of synercid contains 150 mg of quinupristin and 350 mg of Dalfopristin.

Administration – intravenously.

USES In life threatening infections and certain skin

infections. Adverse effects : Pain, swelling and irritation at the injection site. Muscle and joint pain, nausea, vomiting, rash,

diarrhoea, headache, itching.

4. LINEZOLID New antibacterial drug belongs to class

oxazolidones. Inhibits protein synthesis – 70s ribosomes. Active against methicillin resistant and sensitive

staphylococci, and streptococci enterobacteria faecalis.

400 – 600 mg orally twice daily (12 hrly) parenteral route for severely ill patients. Dosage is same as that of oral route

Metabolized by oxidation and hence can safely used in renal failure.

5. MOXIFLOXACIN It is a synthetic fluoroquinolone agent. Inhibits topoisomerase II and IV, there by

affects the replication and repair of bacterial DNA. It is active against following organisms : Step. aureus, staph Epidermides, strepto

pneumonias, H. influenzae, Klebsiella, Enterobacilus, mycobacterium, Bacillus anthracis.

Administrated both oral and intravenous route.

Dose : 400 mg daily orally or i.v. infusion.

USES Acute sinusitis. Acute exacerbation of chronic bronchitis. Pneumonia. Skin and skin structure infections. Second – line agent in T.B.

CONTRAINDICATIONS : Known hypersensitivity, in QT prolongation. Pregnancy and lactation.

SIDE EFFECTS : G.I. disturbances – Nausea vomiting anorexia, bloating.

6. GATIFLOXACIN It is a fourth generation fluro-quinolone

agent. Greater affinity for topoisomerase IV. Active against gram +ve cocci. Oral and intravenous route. Dose – 200 to 400 mg orally or i.v. once daily

(+½ shown) Active against – Streptococcus pneumonias. Chlamydia pneumonias.

INTERCALATING AGENTS

The reversible inclusion of a molecule between two other groups, most commonly seen in DNA

Inhibits DNA replication in rapidly growing cells

ANTHRACYCLINES

First anthracycline antibiotics were isolated from Streptomyces peucetius in 1958

Interact with DNA by intercalcation and inhibit topsoimerase

Some of the most effective cancer drugs availableVery wide spectrum

Common Anthracyclines Daunorubicin (Cerubidine) Doxorubicin (Adriamycin, Rubex) Epirubicin (Ellence, Pharmorubicin) Idarubicin (Idamycin)

DOX vs. DNR Daunomycin (DNR) for acute lymphocytic and myeloid

leukenmia Doxorubicin (DOX) for chemotherapy for solid tumors

including breast cancer, soft tissue sarcomes, and aggressive lymphomas

MECHANISMS OF ACTION Disrupt DNA

Intercalate into the base pairs in DNA minor grooves Inhibits topoiosomerase II enzyme, preventing the relaxing of

supercoiled DNA, thus blocking DNA transcription and replication Cause free radical damage of ribose in the DNA

Negative Effects Causes cardiotoxicity due to free radical

formationInterference with ryanodine receptors of the

sarcoplasmic reticulum in the heart muscle cellsFree-radical formation in the heartLeads to forms of congestive heart failure, often

years after treatment Counteract with dexrazoxane

Bleomycins (BLM) Natural glycopeptidic antibiotics produced

by Streptomyces verticillus Efficacy against tumors Mainly used in therapy in a combination

with radiotherapy or chemotherapy Commonly administered as Blenoxane, a

drug that includes both bleomycin A2 and B2.

History of Bleomycins First discovered in 1966 by Hamao Umerzawa

from Japan when screening cultures of S. verticullus

Launched in Japan by Nippon kayaku in 1969 Initially marketed by Bristol-Myers Squibb

under brand name-Blenoxance

Structure

Mechanism Induction of DNA strand breaks Medicate DNA strand scission of single and

double strand breaks dependent on metal ions and oxygen

Side effects Pulmonary fibrosis and impaired lung

function Age and dose relatedCapillary changes, atypical epithelial cells

Resistance to Anticancer Agents Resistance mechanisms can operate to

Prevent agents from entering cells, as in loss of plasma membrane carriers for nucleoside analogs

Enhance their extrusion, as exemplified by energy-dependent pumps such as ABC transporters

ANTIBIOTICS

NEEDED,NOT

NEEDED

WHAT TO DOWHAT TO GIVE

HOW TO DO

PROBLEMS OF

MISUSE

WHEN THE QUESTION OF USING ANTI BIOTICS ARISES IN MAXILLOFACIAL SURGERY????

SURGICAL EXTRACTIONS SURGIAL MANAGEMENT OF LESIONS SPACE INFECTIONS TRAUMA ORTHOGNATHIC SURGERY OSTEOMYELITIS

[ ASIAN J OMFS : VOL 18 : NO. 4 : 272-278 ]

MOST ORAL INFECTIONS ARE ODONTOGENIC IN ORIGIN

SEQUELAE OF DEEP CARIOUS LESION / PERIODONTAL / PERICORONAL INFECTIONS

MANAGEMENT

EXTRACTION / ENDO TREATMENT

/ SURGICAL DRAINAGE

WITHOUT ANTIBIOTICS

CONCLUSION

UNCOMPLICATED EXTRACTION,SURGERIES +

OTHERWISE HEALTHY

LOW INFECTION RATE

ANTIBIOTICS NOT NEEDED

[ JIDA VOL.69 : SEPT-DEC 1998 : 274 – 277]

CONCLUSION Antibiotics are used to treat infections and

are also responsible for making them more difficult to treat because of their misuses and development of resistance. The only way to keep antibiotics useful is to use them appropriately and judiciously.

NEVER ACCEPT CONCEPT OF ANTIBIOTICS ON DEMAND

NEVER USE A BROAD SPECTRUM ANTIBIOTICS WHEN NARROW SPECTRUM IS INDICATED

NO LONG COURSE OF ANTIBIOTICS

NO NEED OF ANTIBIOTIC PROPHYLAXIS FOR SIMPLE SURGICAL PROCEDURES or WHEN THERE IS LESS CHANCE OF POST SURGICAL INFECTION

WHEN NO SIGNS OF INFECTIONS SUCH AS SWELLING,LYMPHADENOPATHY, ELEVATED TEMPERATURE

ALWAYS MAKE SURE THE SOURCE OF INFECTION IS ELIMINATED-EXTRACTION OF TOOTH

INCISION AND DRAINAGE

REFERENCES Medical pharmacology - Satoskar Medical pharmacology. - K.D. Tripathi.

Contemporary oral and maxillofacial surgery. - Lary J. Peterson 4th Edition. Pharmacology and therapeutics and dentistry. - Yogiela Dowd Neidle

OMFS Clin N Am -2003 Oral and maxillofacial infections

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Antibiotics in Oral and Maxillofacial Surgery

Health & Medicine