ANTIMICROBIALS

DR PADMAVATHI S

ANTIBIOTICS OR ANTIMICROBIALS ???

HISTORY

• Mouldy curd boils• Chaulmoogra oil leprosy• Mercury syphilis• Cinchona bark fever• Ehrlich’s phase of dye

• PENICILLIN DISCOVERY

Classification BASED ON • Chemical structure• Mechanism of action• Type of organism against which primarily active• Spectrum of activity• Type of action• Source

Chemical StructureSulfonamides – sulfadiazine , dapsoneDiaminopyridines – trimethoprim, pyrimethamineQuinolones – nalidixic acid, ciprofloxacinBeta lactums – penicillins, cephalosporinsNicotinic acid derivative – isoniazid, pyrazinamide, ethionamideAzole derivatives – miconazole, ketoconazoleMacrolides – azithromycin, clarithromycin

Mechanism of action• Cell wall synthesis inhibitors – penicillin, cephalosporin• Leakage of cell membranes – amphotericin B• Protein synthesis inhibitors – tetracyclines, macrolides• Inhibit DNA gyrase - Fluoroquinolones• Interfere DNA function – rifampicin • Interfere with intermediary metabolism – sulfonamides

Type of organism against which primarily active• Antibacterial • Antifungal• Antiviral• Antiprotozoal• Anthelmintic

Spectrum of activity• Narrow spectrum

• Broad spectrum

Type of action•Bacterio static

•Bacterio cidal

Sources • Fungi – penicillin

• Bacteria – polymyxin B

• Actinomycetes – aminoglycosides

Problems • Toxicity• Hypersensitivity reactions• DRUG RESISTANCE• Superinfection• Nutritional deficiencies• Masking of an infection

Drug resistance• Unresponsiveness of a microorganism to an antimicrobial agent• Natural & acquired • Mutation / gene transfer• Stable & heritable genetic change – spontaneously & randomly

– vertical transfer

• Drug tolerant• Drug destroying• Drug impermeable

CROSS RESISTANCE

• Resistance to one AMA conferring resistance to another AMA• to which the organism has not been exposed• Complete• Partial

• No indiscriminate use• Prefer narrow spectrum drugs• Combination of drugs

Superinfection/ Suprainfection • Appearance of new infection as a result of antimicrobial therapy

• Broad & extended spectrum antibiotics

• Tetracycline, chloramphenicol

Predisposing factors• Corticosteroid therapy• Malignancy• AIDS• Agranulocytosis• Diabetes mellitus

Examples of superinfection• Candida albicans – oral thrush, vulvovaginitis• Resistant staphylococci enteritis• Clostridium difficile – pseudomembranous enterocolitis

treatment - vancomycin / metronidazole• Proteus – urinary tract infection• Pseudomonas – UTI, enteritis

Toxicity • Local irritancy

• Systemic toxicity• Aminoglycosides – ototoxicity• Chloramphenicol – bone marrow suppression• Amphotericin B – nephrotoxicity

Hypersensitivity reactions• Rashes• Anaphylactic shock

• Sulfonamides• Penicillins• Cephalosporins

Masking of an infection• Syphilis masked by single dose penicillin used for gonorrhea