ANTIBIOTICS IN MAXILLOFACIAL SURGERY

Presenter : Dr. Venu G.R. Moderator : Dr. Raghavendra

CONTENTS
Introduction & History Classification of antibiotics Microbiology of head & neck infections. Pharmacology of antibiotics Adverse effects of antibiotics Empirical therapy of head & neck infections. General principles of antibiotic selection General principles of antibiotic administration. Prophylactic use of antibiotics. Conclusion.

History
PHASE I : Phase of Empirical Use: (16th & 17th cen.) - Mouldy curd on boils Chinese - Chaulmoogra Oil in leprosy Indians - Chenopodium in intestinal wormsAztecs - Mercury for syphilis PHASE II : 1854-1935 - The "dawn" of modern antimicrobial therapy Paul Ehrlich - 1906: Arsphenamine for syphilis 1909: Atoxyl for sleeping sickness

History
PHASE III: Modern Era 1928: Sir Alexander Fleming Staphylococcus aureus cultures. Penicillium. Inhibition of the bacterial colonies near the mold

1935:

Domagk used sulfonamide dye for pyogenic infection. Sulfapyridine was marketed.

1938:

History
WW II provided the incentive for both British and then American scientists to develop penicillin from the fungus. 1940's: The miracle drug was introduced on a large scale.

Terminology
Antibiotic A chemical substance produced by molds or bacteria that kills or inhibits the growth or other microorganisms. This refers to natural compounds only, not chemically synthesized compounds. Antimicrobial This term refers to both antibiotics and synthetic agents active against microbes. Microcidal (Bacteriocidal. Vircidal, 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. Destruction - 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. Broad Spectrum Antimicrobial: An antimicrobial that acts on a wide range of species.

MICROBIOLOGY OF HEAD AND NECK INFECTIONS

Isolates

No. of Times Isolated

Aerobic species
Gram-positive cocci Alpha-hemolytic streptococci S epidermidis Streptococci (unspecified) Beta-hemolytic streptococci S aureus Gram-negative cocci Gram-positive rods Gram-negative rods Anaerobic species Gram-positive cocci Peptococcus Peptostreptococcus Streptococcus (other) Gram-negative cocci Veillonella Gram-positive rods Eubacterium 29 19 82 62 Occasionally 91 31 21 15 12 Rare Rare

Rare

Actinomyces
Propionibacterium Gram-negative rods Bacteroides Fusobacterium

20
10

196 54

J Oral Maxillofac Surg 47:976-985,1989

Bacteria Isolated
No. Isolated from 1980s patients (% of total) No. Isolated From 1990s Patients (% of total) X2 P

Gram positive cocci Other gram positive bacteria

101 (56) 9 (5)

80 (70) 5(4)

5.35 0.066

.021 .8

Gram negative anaerobes

41 (25)

15 (13)

4.323

.038

Other gram negative bacteria Total isolates

29 (16)

15 (13)

0.520

.5

180 (100)

115 (100)

The changing face of Odontogenic infections: J Oral Maxillofacial Surgery 59:739-748,2001

Comparison of Bacteria Identified from both patient groups

Bacteria
Gram-positive cocci Alpha-Hemolytic streptococci Beta-hemolytic streptococci Staphylococcus aureus Coagulase-negative epidermidis Staphylococcus epidermidis Gama Hemolytic streptococci Preptostreptococcus sp Enterococcus sp 47 22 12 15 2 3 1 24 21 8 18 5 3 1 9.900 0.055 0.498 22-59 14.9-9 0.846 0.000 0.005 0.002 0.815 0.480 0.001 0.001 0.358 1.000 0.95No. of 1980s patients No. of 1990s patients

X2

Other gram-positive bacteria Diptheroids Actinomyces sp Lactobacillus sp Corynebacterium sp Gram negative anaerobes Bacteroides melaninogenicus Bacteriodes ( lactamase +) Bacteriodes ( lactamase -) Bacteroides (not fragilis) Fusobacterium necrophorum Bacterides fragilis .. Total 27 1 6 4 2 2 1 29.59 1.928 2.660 0.622 0.622 0.000 0.001 0.03 0.103 0.430 0.430 1.000 6 2 1 4 1 0.025 0.406 0.000 0.003 0.8-8 0.524 1.000 0.95-

180

115

Major pathogens of head and neck infections

Type of infection
Odontogenic cellulites/abscess

Microorganisms
Streptococcus milleri group Peptostreptococci Prevotella and Porphyromonas Fusobacteria Acute Streptococcus pneumoniae Haemophilus influenzae Head and neck anaerobes (peptostreptococci, Prevotella Porphyromonas, fusobacteria) Group A beta-hemolytic streptococci Staphylococcus aureus Morahella catarrhalis Viruses Head and neck anaerobes

Rhinosinusitis

Chronic

Fungal

Aspergillus Rhizopus sp. (mucor) Enterobacteriaceae (especially Pseudomonas, Acinetobacter, Escherichia coli) S. Aureus Yeasts (Candida species)

Nosocomial (especially if intubated)

Oral and Maxillofacial Surgery Clinics of NA :2003

Major pathogens of head and neck infections

Osteomyelitis of the jaws Acute Odontogenic flora S. aureus and skin flora in trauma Salmonella in sickle cell disease

Chronic

Actinomyces species

Necrotizing fasciitis

Group A beta-hemolytic streptococci regional flora (oral and sinus pathogens in head and neck) Mucosal or disseminated Candida species

Fungal

Soft tissue

Histoplasma species Blastomyces species

Aspergillus Rhizopus (mucor)

Sinus

Oral and Maxillofacial Surgery Clinics of NA :2003

CLASSIFICATION

Chemical structure
1. 2. 3. 4. Sulfonamides and related drugs: Sulfadia-zine and others, Sulfones Dapsone (DDS), Paraaminosalicylic acid (PAS). Diaminopyrimidines: Trimethoprim, Pyrimethamine. Quinolones: Nalidixic acid, Norfloxacin, Ciprofloxacin etc. -lactam antibiotics: Penicillins,Cephalosporins, Monobactams, Carbapenems. Tetracyclines: Oxytetracycline, Doxycycline etc. Nitrobenzene derivative: Chloramphenicol. Aminoglycosides: Streptomycin, Gentamicin, Neomycin etc. Macrolide antibiotics: Erythromycin, Roxithromycin, Azithromycin etc. Polypeptide antibiotics:Polymyxin-B, Colistin, Bacitracin, Tyrothricin. Glycopeptides : Vancomycin, Teicoplanin Oxazolidinone: Linezolid. Nitrofuran derviatives: Nitrofurantoin, Furazolidone. Nitroimidazoles:Metronidazole, Tinidazole. Nicotinic acid derivatives: Isoniazid, Pyrazinamide, Ethionamide. Polyene antibiotics: Nystatin, Amphote-ricin-B, Hamycin. Azole derivatives: Miconazole, Clotrimazole, Ketoconazole, Fluconazole. Others: Rifampin, Lincomycin, Clindamycin, Spectinomycin, Sod. fusidate, Cycloserine, Viomycin, Ethambutol, Thiacetazone, Clof azimine, Griseofulvin.

5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.

Type of organisms against which primarily active

Antibacterial: Penicillins, Aminoglycosides, Erythromycin etc. Antifungal: Griseofulvin, Amphotericin B, Ketoconazole etc. Antiviral: Idoxuridine, Acyclovir, Aman-tadine, Zidovudine etc. Antiprotozoal: Chloroquine, Pyrimethamine, Metronidazole, Diloxanide etc. Antihelmintic: Mebendazole, Pyrantel, Nic-losamide, Diethyl carbamazine etc.

Spectrum of Activity
Narrow Spectrum: Penicillin G Streptomycin Erythromycin Broad Spectrum: Tetracyclines Chloramphenicol

Type of Action
Primarily bacteriostatic: Sulfonamides Chloramphenicol Ethambutol Tetracyclines Erythromycin,

Primarily bactericidal: Penicillins Aminoglycosides Polypeptides Rifampin Cotrimoxazole

Cephalosporins Vancomycin Nalidixic acid Ciprofloxacin

Antibiotics are obtained from

Fungi: Penicillin Cephalosporin Bacteria: Polymix B Colistin Bacitracin Tryothricin Actinomycetes: Aminoglycosides Tetracyclines Chloramphenicol Macrolides

Mechanism of action
1. Inhibit cell wall synthesis: Penicillins, Cephalosporins, Cycloserine, Vancomycin, Bacitracin. 2. Cause leakage from cell membranes: PolypeptidesPolymyxins, Colistin, Bacitracin. PolyenesAmphotericin B, Nystatin, Hamycin. 3. Inhibit protein synthesis: Tetracyclines, Chloramphenicol, Erythromycin, Clinda-mycin, Linezolid. 4. Cause misreading of m-RNA code and affect permeability: AminoglycosidesStreptomycin, Gentamicin etc. 5. Inhibit DNA gyrase: Fluoroquinolones Ciprofloxacin. 6. Interfere with DNA function: Rifampin, Metronidazole. 7. Interfere with DNA synthesis:Acyclovir, Zidovudine. 8. Interfere with intermediary metabolism: Sulfonamides, Sulfones, PAS, Trimethoprim, Pyrimethamine, Ethambutol.

PHARMACOLOGY

CELL WALL SYNTHESIS INHIBITORS

Penicillins Cephalosporins Cycloserine Vancomycin Bacitracin

PENICILLINS
First used in 1941, called the miracle drug. Originally form Penicillium notatum. High yielding mutant P.chrysogenum.

MOA: Interfere with the synthesis of bacterial cell wall. Inhibits transpeptidase (closed knit structure). Cell wall deficient (CWD) forms.

PENICILLIN-G (BENZLY PENICILLIN)

- Narrow spectrum - Gram +ve bacteria Cocci: - Streptococci - Staph. aureus - Nesseria gonorrhoeae, N. menigitidis (G ve) Bacilli: - Coryebacterium diphtheriae - All Clostrida

PENICILLIN-G (BENZLY PENICILLIN)

Penicillin resistance: Penicillinase Opens - lactam ring Staphylococci, E.coli, H.influenzae

PENICILLIN-G (BENZLY PENICILLIN)

Acid labile Poorly cross CSF T is 30 mins Distributed extracellularlly

Preparations and dose:

Penicillin G Inj.

0.5-5 MU i.m/i.v

6-8 hrly

Repository Penicillin G: (i.m only) 1. Procaine penicillin G: 0.5-1 MU 2. Benzathine penicillin G: 0.6-2.4 MU 12-24 hrly 2-4 weekly

PENICILLIN-G (BENZLY PENICILLIN)

Adverse Effects: Local irritancy and direct toxcity Hypersensitivity
1-10% incidence Rash, itching, urticaria and fever Restricted use.

Superinfection Jarisch-Herxheimer reaction

Syphilitic patients Shivering, fever, exacerbation of lesions. 12-72 hrs

PENICILLIN-G (BENZLY PENICILLIN)

Uses:
Streptococcal Infections: Pharyngitis Otitis media Scarlet fever Rheumatic fever If sensitive 3-6 MU i.v 6th hrly

Pneumococcal Infections: Meningococcal Infection Gonorrhoea Syphilis Diphtheria Tetanus and gas gangrene

SEMISYNTHETIC PENICILLINS
Benzyl side chain To overcome
Poor oral efficacy Susceptibility to penicillinase Narrow spectrum of activity Hypersensitivity (not yet)

Classification: 1. Acid resistance: Phenoxymethyl penicillin (Penicillin V) 2. Penicillinase resistant penicillins: Methicillin 3. Extended spectrum penicillins: Ampicillin, Amoxicillin, Piperacillin

BETA-LACTAMASE INHIBITORS
Clavulanic Acid Sulbactum
Clavulanic acid : It has a lactam ring but no antibacterial activity on its own. Inhibits wide variety of lactamases. Progressive inhibitor. Suicide inhibitor. T1/2 & tissue distribution matches with amoxicillin. Used against lactamase producing resistant staph. aureus (but not MRSA)

Augmentin: amoxicillin 250mg + clavulanic acid 125mg tab: 1-2 tab TDS. Imipenem : ex Carbapenem

BETA-LACTAMASE INHIBITORS
Sulbactum:
Semisynthetic lactamase inhibitor. It is 2-3 times less potent than clavulanic acid. Combined with ampicillin. Dosage : Ampicillin 1gm + sulbactum 0.5gm per vial inj : 1-2 vial deep IM/IV inj 6-8 hrly.

CEPHALOSPORINS
Closely related to the penicillins. Have a beta lactam ring as part of the basic structure (cephalosporanic acid). Differ from each other in their side chains (R groups).

CEPHALOSPORINS
Examples
First Generation Cefazolin Cephradine Cephalexin Cefadroxil Cephapirin Second Generation Cefuroxime Cefaclor Cefonicid Cefpodoxime Cefprozil Cefoxitin Cefotetan Cefmetazole Third Generation Cefotaxime Ceftriaxone Ceftazidime Cefixime Cefoperazone Ceftibuten Ceftizoxime Cefdoren Cefdinir

Useful Spectrum
Is active against streptococci Is active against staphylococcus aureus Is not active against enterococci, Listeria, or MRSA

Expands first-generation spectrum to include greater gram-negative activity (Haemophilus influenzae, including ampicillin-resistant strains, and Escherichia coli, Neisseria, Klebsiella, Acinetobacter, Enterobacter, Gitrobacter, proteus, providencia, and moraxella. Is not as active against gram positive organisms as first-generation; not active against enterococci, Listeria, MRSA or Pseudomonas Has spectrum similar to that of cefuroxime, but also active against Bacteroides fragilis, bacteroides spp., and other anaerobes. Achieves therapeutic concentrations in CSF, unlike first and second Gen. Is less active than first generation against gram-positive bacteria; less active than cefoxitin or cefotetan against anaerobes. Has expanded gram-negative spectrum compared with first and second generations, including Citrobacter, E coli, Klebsiella, Enterobacter, Pseudomonas aeruginosa, Proteus, Morganella, Providencia, Serratia, Neisseria Gonorrhoeae. Is not active against enterococci, Listeria, or MRSA. Is more effective than oral third-generation antibiotics (Cefixime, Cefpodoxime), which lack useful activity against most strains of Enterobacter and Pseudomonas and have limited antianaerobic activity. Compares with that of third generation but more resistant to some extended-spectrum -lactamases

Fourth Generation Cefepime

VANCOMYCIN
Relatively toxic antibiotic most primarily for the treatment of MRSA. Has no activity against G-ve bacteria. It is administered intravenously but requires a very slow infusion. Causes RED MAN SYNDROME
Flushing, prurities, dyspnea, muscle spasm and chest pain.

Other toxic effects are nephrotoxicity, ototoxicity.

Dosage: Normal pts 2g/day BID / QID Pts with renal compromise creatinine clearance values.

DRUGS CAUSING LEAKAGE FORM CELL MEMBRANES

Polypeptides: Polymyxins Colistin Bacitracin Polyenes: Amphotericin B Nystatin Hamycin

Amphotericin B (AMB)
Has broad spectrum Candida species, dermatophytes, aspergillus, Rhizopus and Mucor spp. Treatment of choice for life threatening mycotic infections. In head & neck AMB is used for severe sinusitis, cavernous sinus thrombosis, orbital apex syndrome and otitis externa caused by fungal organisms.

Amphotericin B (AMB)
MOA: By increasing the cellular permeability. Dosage and mode of administration: Test dose: 1mg in 250 ml 5% dextrose over 2-4hrs. Thereupetic dose :5mg in 500ml 5%dextrose over 4-6hrs. There after the dose is increased by 5mg daily until a dose of 0.4-0.75 mg/kg/d is reached.

The drug is given intravenously and titration from a low to therapeutic index is performed over several days while renal function is monitored.

Amphotericin B (AMB)
Adverse Effects:

Occurs with each infusion

chills, fever, aches, pain, nausea, vomiting etc. due to release of cytokines (IL, TNF).

Intensity of reaction decreases with continued medication.

Inj. Hydrocort 0.6mg/kg. Thrombophelibits of injected vein. Nephrotoxicity, anemia, CNS toxicity

NYSTATIN
Similar to AMB Higher systemic toxicity, so used locally Uses: Oral thrush Dose: 1 lac unit tab in glycerne Oral candidiasis Corneal candidiasis No resistance observed

DRUGS WHICH INHIBIT PROTEIN SYSTHESIS

Tetracyclines Chloramphenicol Erythromycin

Clindamycin
Linezolid

TETRACYCLINES
Broad spectrum Bacteriostaic. Inhibit protein synthesis by binding to 30S ribosomes. Not used much in OMFS. Doxycyclines & minocyclines recent tetracyclines used now to some extent.

TETRACYCLINES
Antimicrobial Spectrum: Initially board spectrum Most gram positive bacilli Some gram negative bacilli: V.cholerae, Helicobacter pyroli Resistance: Pump out Protection protein Administration and Dose: Oral tablets i.m. is painful Slow i.v.

TETRACYCLINES
ADRs: Irritative effects Liver damage Kidney damage Phototoxicity Teeth and Bones
Midpregnancy-5 month extrauterine : deciduous 3 mon 6yrs : Permanent anteriors

Vestibular toxicity

CHLORAMPHENICOL
1947, Streptomyces venezuelae Nitrobezene component: antibacterial activity, intense bitter taste. MOA: Interfering transfer of elongating peptide chains Permeability of cell wall Lower affinity of bacteria ribosome Uses: Never used for minor infections Enteric fever H.influenzae meningitis Anaerobic infections UTI

CHLORAMPHENICOL
ADRs: Bone marrow depression Hypersensitivity Gray baby syndrome
- high dose ~100mg/kg, stops feeding, vomiting, hypothermic, abdomen distension, irregular respiration, gray cyanosis - Blocks electron transport - ~25mg/kg/day

Superinfections Irritative effects

ERYTHROMYCIN
Macrocyclic lactone ring Used since 1950s MOA: Bacteriostatic at low and cidal at high concentrations. Interfering with proteins synthesis by attaching to the 50s ribosomes.

Spectrum:
Its gram +ve antibacterial properties are similar to those of penicillins but not as effective as penicillins against anaerobes.

Can be used in patients allergic to penicillins.

ERYTHROMYCIN
Resistance: Less permeable to erythromycin ADRs: GIT
- Motilin receptor

Hypersensitivity
Doses: 250-500 mg 6th hrly for adults 30-60 mg/kg/day for children

VANCOMYCIN
Glycopeptide antibiotic Discovered in 1956 MOA: Inhibiting cell wall synthesis Dipeptide D-ala-D-ala sequence

Spectrum: Very effective against MRSA Strep. viridans Enterococcus No activity against G+ve bacteria

VANCOMYCIN
Toxicity: Rapid i.v. Red Man Syndrome
Chills, fever, urticaria and intense flushing

Nerve deafness Nephrotoxicity Hypotension Pseudomembranous colitis

Dose: 500 mg 6th hrly infused i.v over 1 hr OR 1 gm 12th hrly infused i.v over hr
Precautions: Renal function test Hearing function test

5% dextrose

VANCOMYCIN
DOSAGE TABLE FOR VANCOMYCIN IN PATIENTS WITH IMPAIRED RENAL FUNCTION (Adapted from Moellering et al) Creatinine Clearance mL/min 100 90 80 70 60 50 40 30 20 10 Vancomycin Dose mg/24 h 1,545 1,390 1,235 1,080 925 770 620 465 310 155

The initial dose should be no less than 15 mg/kg, even in patients with mild to moderate renal insufficiency.

DRUGS CAUSING MISREADING OF m-RNA CODE AND AFFECT PERMIABLILITY

Aminoglycosides Streptomycin Gentamicin Neomycin Amikacin Kanamycin

AMINOGLYCOSIDES
MOA: i. Transport of the aminoglycoside through the bacterial cell wall and cytoplasmic membrane. Binding to ribosomes resulting in inhibition of protein synthesis.

ii.

Mech. Of Resistance: i. Acquisition of cell membrane bound inactivating enzymes. ii. Mutation decreasing the affinity of ribosomal proteins that normally bind the aminoglycoside. iii. Decreased efficiency of the aminoglycoside transporting mechanism.

AMINOGLYCOSIDES
Shared Toxicities: Ototoxicity - Cochlear damage - Vestibular damage Nephrotoxicity Neuromuscular blockade Precautions: Avoid during pregnancy Avoid using other concurrent oto/nephrotoxic drugs Kidney damage Do not mix aminoglycoside with any drug in same syringe/ infusion bottle

STREPTOMYCIN
Oldest aminoglycoside. Its spectrum is relatively narrow, primarily aerobic G-ve bacilli. Some G+ve cocci, in high concentration. Streptomycin dependence ADRs: Vestibular disturbances Lowest nephrotoxicity Pain at injected site Exofoliative dermatitis

Uses: Tuberculosis Sub Acute Bacterial Endocarditis (SABE) Plague

GENTAMICIN
1964 T 2-4 hrs Broader spectrum of action Infective against M.tuberculosis, Strep.aureus, Strep.faecalis. Relatively more nephrotoxic. Dose: According to body weight. Adult with normal renal function (creatinine clearance >/= 100ml/min): 3-5 mg/kg/day i.m. either single dose or divided in three doses for 8th hrly.

AMIKACIN
Semisynthetic derivative Resistant to bacterial aminoglycoside inactivating enzymes Widest spectrum of activity

Dose: 15mg/kg/day in 1-3 doses

NEOMYCIN
Wide spectrum aminoglycoside Active most G -ve bacteria and +ve cocci Highly toxic to internal ear and kidney Poorly absorbed from GIT Uses: Topically Orally: Preparation of bowel before surgery Dose: 0.25-1gm QID orally 0.3-0.5% topical.

DRUGS WHICH INHIBIT DNA GYRASE

Fluoroquinolones Ciprofloxacin Norfloxacin Nalidixic acid

CIPROFLOXACIN
Broad spectrum Most susceptible: Aerobic G ve bacilli, Neisseria, enterobacteriaceae Widely used in OMFS MOA: Inhibit bacterial DNA gyrase Nicks double stranded DNA Negative supercoiling No replication/transcription

CIPROFLOXACIN
Uses: UTI Gonorrhoea Bacterial gastroenteritis Typhoid (drug of choice) Bone, soft tissue and wound infections Respiratory infection Meningitis

DRUGS WHICH INTERFERE WITH DNA FUNCTION

Metronidazole Rifampin Tinidazole

METRONIDAZOLE
Nitroimadazole, 1959 against protozoa. Selectively toxic to anaerobic microorganisms.

MOA: Enters cell by diffusion DNA damage (cytotoxicity) DNA helix destabilization Strand breakage

METRONIDAZOLE
Uses: Anaerobic bacterial infections Ulcerative gingivitis, trench mouth Pseudomembranous enterocolits Amoebiasis Helicobacter pylori gastritis/peptic ulcer Doses: 200-400 mg tab 8th hrly 500 mg/100 ml i.v. infusion

ANTIBIOTIC RESISTANCE

Antibiotic resistance refers to the unresponsiveness of a micro org to an antimicrobial agent & is akin to the phenomenon of tolerance seen in higher animals.

How does antibiotic resistance arise?

1. 2. 3. 4. Alteration of a drugs target site Inability of a drug to reach its target Inactivation of an antimicrobial agent Active elimination of an antibiotic from the cell

Mech. Of acquiring resistance genes: Spontaneous mutation Gene transfer Bacteriophages Mosaic genes

Conjugation

Transduction

Transformation

DRUG TOLERANT : Loss of affinity of the target biomolecule of microorgainsm Eg: Penicillin resistant pneumococcal strains have altered PBP
DRUG DESTROYING: Inactivates the drug Eg. B. lactamases produced by staph, haemophilus inactivate Pen G DRUG IMPERMEABLE: Porins Eg. Pen. resistant gonococci are less permeable to Pen G.

PREVENTION OF DRUG RESISTANCE

No indiscriminate & inadequate or unduly prolonged or sub therapeutic doses to be administered. Prefer rapidly acting & narrow spectrum when ever possible. Use combination of AMA when prolonged therapy is undertaken. Eg: TB

Organisms notorious for developing resistance must be treated intensively Eg: Staph. aureus, E.coli

PRINCIPLES OF ANTIBIOTIC SELECTION

I. Patient factor :
1. Age
Neonates: Chloramphenicol : Gray baby syndrome Sulfonamides : Kernicterus Elderly : Aminoglycosides : VIII nerve toxicity

2. Renal and hepatic function

Renal : Cehalathin, Cephaloridine, Tetracycline Hepatic : Tetracyclines, Erythromycin, Pyazinamide.

3. Local factors
Pus, necrotic material, lower pH, anaerobic abscess center.

4. Drug allergy 5. Impaired host defence

II. Organism related consideration: 1. Clinical diagnosis itself directs the choice 2. Good guess 3. Choice to be based on bacteriological examination
i. Bacteriological services not available ii. Bacteriological services available, but treatment cant be delayed. iii. Bacteriological services available, but treatment can be delayed.

III. Drug factors: 1. Spectrum of activity 2. Type of activity 3. Sensitivity of organism 4. Relative toxicity 5. Pharmacokinetic factors 6. Evidence of clinical efficacy 7. Cost

IV. Special conditions:

1. Pregnant women
Chloramphenicol: Gray baby syndrome Ciprofloxacin: Possibility of joint abnormalities (seen only in animals) Kanamycin Streptomycin: Damage to the fetus's ear, resulting in deafness. Sulfonamides: Jaundice and possibly brain damage in the newborn. The breakdown of red blood cells. Tetracycline: Slowed bone growth, permanent yellowing of the teeth, and increased susceptibility to cavities in the baby. Congenital defects.

Safer drugs during Pregnancy

Penicillins Cephalosporins Erythromycin Azithromycin Clindamycin Clotrimazole

2. Lactating women
(1) Safe for administration:
Aminoglycosides. Amoxycillin. Amoxycillin-clavulanate. Antitubercular drugs. Cephalosporins. Macrolides. Trimethoprim-sulphamethoxazole.

(2) Effects not known/to be used with caution:

Chloramphenicol. Clindamycin. Dapsone. Penicillins. Tetracyclines.

(3) Not recommended:

Metronidazole (single high dose). Quinolones.

3. Children
Based of child's body surface area (BSA) Childs dose = BSA of Child X adult dose 1.73 m Clarks Rule: (wt) Wt. in kg X adult dose 70 Oral, Rectal, Nasal, Oral transmucosal, Intravenous, intramusular a. b. c. Tetracyclines causes permanent dental staining. Floroquinolones causes chondrotoxicity in the growing cartilage. Imepenem Tendency to cause seizures.

4.Geriatrics
Physiology of aging
Gastrointestinal, Metabolic, CNS , CVS, RS, Renal & liver function Changes

Dosage modification: 1/3rd to the dose of normal adult Single dose for short term Therapies should be limited to 5-10 days. Avoid intravenous drugs

Jor. American Dental Asso. 47-54, 1999.

5. Immunocompromised Patient
Diabetes mellitus Alcoholism HIV infected patients Start empiric antibiotics Culture sensitivity test Surgical debridement Incision and drainage Removal of all nidi (teeth, necrotic tissue, nonvital bone) Exploration and irrigation of all involved facia Proper wound care

Immunocompromised Patient
Antibiotics: High dose Broad spectrum
Aggressive surgical incision and drainage Frequent irrigation

Empirical antibiotic therapy: Penicillin Clindamycin 1st generation cephalosporins

PRINCIPLES OF ANTIBIOTIC ADMINISTRATION

1. Proper dosage
MIC Dosage : 3-4 times the MIC.

2. Proper route of administration

Depends mostly on the severity of infection

PRINCIPLES OF ANTIBIOTIC ADMINISTRATION

3. Consistency in route of administration:
Maintenance of peak blood levels of AMA for an adequate period is imp. to achieve max tissue penetration & effective bacterial killing.

4. Combination therapy:
Indications: A) To increase antibacterial spectrum - in unknown cause B) To increase bactericidal effect.

Drug interactions
The 2 important category of drug interactions : i) antibiotic interfence with the effectiveness of oral contraceptives. ii) antibiotic interference with metabolism of drugs which involve the cyt P450 system. The enzymes in this system are CYP3A4, CYP2C19, CYP2D6

Empirical therapy

Prophylactic use of antibiotics

Basic principles :
1. Significant risk of infection: Alteimer et al classified surgical wounds: a) clean b) clean-contaminated c) contaminated or dirty Modified classification : For oral cavity wounds. 1) clean surgical wounds 2) clean contaminated surgical wounds 3) contaminated

2. Antibiotic selection: Oral contamination :

Sinus & Nose : Skin : 3. Antibiotic administration : Normal patient:

Streptococci, Anaerobic G-ve rods , Anaerobic G+ve cocci H influenza, Diphtheroides, Peptostreptococci. Staph. aureus & epidermidis.

I.V / I.M within 30min of incision time at twice therapeutic dose. Penicillin - 2 MU Cephazolin 1 gm (skin) 4th hrly. Medically compromised pts: Until biologic sealing.

Adjunctive procedures
- Adequate cleansing of surgical site - Strict adherence to sterile technique - Avoiding tissue trauma - Minimizing operating time - NOT to shave the region, evening before surgery - Closed-suction drains in non-infected wounds - NOT to be placed from the surgical incision

Oral and Maxillofacial Surgery Clinics Of NA, Feb 2003.

Endocarditis prophylaxis recommended

Dental extractions. Periodontal procedures such as surgery, scaling, root planing.

Endocarditis prophylaxis NOT recommended

Filling cavities and other restorative dentistry not resulting in bleeding.

Probing and maintenance.

Placement of dental implant and reimplantation of avulsed teeth. Root canal instrumentation or surgery beyond apex. Subgingival placement of antibiotic fibers/strips Initial placement of orthodontic bands (but not brackets).

Local, non-intraligamentary anaesthetic injection

Placement of rubber dams. Postoperative suture removal. Placement or removal of prosthodontic or orthodontic material.

Taking of oral impression (only without retraction Taking of oral radiographs. Fluoride treatment. Shedding of primary teeth.

Intraligamentary local anaesthetic injections.

Prophylactic cleaning of teeth or implants involving bleeding.

Jor. Of Schweiz Med Wochenschr 2000; 130: 27/28

Endocarditis

Jor. Of Schweiz Med Wochenschr 2000; 130: 27/28

CONCLUSION
Antibiotic selection remains as much an art as it is a science.

Although antibiotics do not prevent all post operative infections, they can reduce the incidence significantly when administered correctly.
Future treatment strategies will not only include aggressive use of traditional management methods but also understanding normal immune system and associated defects, new antimicrobials. Ultimately, we should provide a shorter course of treatment and improved outcomes for our patients.

REFERENCES
1. Medical pharmacology, by K.D. Tripathi, 5th edition. 2. Oral & Maxillofacial infections - Topazian 3.Oral & Maxillofacial Clinics of North America, titled, Current Concepts in the management of Maxillofacial Infections, Feb. 2003. 4. Oral & Maxillofacial Clinics of North America, titled, Pharmacology, Feb 2001. 5. Medical problems in Dentistry Cawson & Scully. 6. Antibiotic & Chemotherapy Francis O Grady Harold P.Lambert

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