Antimicrobial Agents: General Principles covers antimicrobial agents — general principles for INI CET (AIIMS PG).
Key Definitions:
- Bacteriostatic: Inhibits bacterial growth (not killing) — tetracyclines, macrolides, sulfonamides
- Bactericidal: Kills bacteria — penicillins, cephalosporins, aminoglycosides, fluoroquinolones, metronidazole
- Minimum Inhibitory Concentration (MIC): Lowest drug concentration that prevents visible bacterial growth
- Minimum Bactericidal Concentration (MBC): Lowest drug concentration that kills 99.9% of bacteria
- Breakpoint: MIC threshold defining susceptible (S) vs resistant (R)
Classification of Antimicrobials:
1. Cell Wall Synthesis Inhibitors (most are bactericidal):
- β-lactams: Penicillins, Cephalosporins, Carbapenems, Monobactams
- Glycopeptides: Vancomycin, Teicoplanin
- Others: Daptomycin (lipopeptide — disrupts membrane)
2. Protein Synthesis Inhibitors (bacteriostatic — except aminoglycosides):
- 30S inhibitors: Aminoglycosides (bactericidal), Tetracyclines (bacteriostatic)
- 50S inhibitors: Macrolides (azithromycin, clarithromycin), Lincosamides (clindamycin), Chloramphenicol, Linezolid (oxazolidinone)
3. Nucleic Acid Synthesis Inhibitors:
- Folate pathway: Sulfonamides, Trimethoprim (separate steps — synergistic)
- DNA gyrase/topoisomerase IV: Fluoroquinolones (bactericidal)
- RNA polymerase: Rifampin (bactericidal — used in TB)
- DNA: Metronidazole (bactericidal — anaerobes)
4. Cell Membrane Disruptors:
- Polymyxins (colistin — last resort for gram-negatives)
- Daptomycin (gram-positive)
5. Anti-TB Agents: Isoniazid, Rifampin, Pyrazinamide, Ethambutol, Streptomycin
6. Anti-Fungal: Polyenes (amphotericin B, nystatin), Azoles, Echinocandins, Flucytosine
Selective Toxicity: The fundamental principle — drug must be more toxic to the pathogen than to the host.
- Human cells lack cell walls → β-lactams are selectively toxic to bacteria
- Bacterial ribosomes (70S) differ from human (80S) → aminoglycosides selectively target bacterial protein synthesis
- Fungal ergosterol vs human cholesterol → polyene antifungals selectively toxic to fungi
Spectrum of Activity:
- Narrow spectrum: Single organism group (e.g., penicillin G — mostly gram-positive cocci)
- Broad spectrum: Multiple organism groups (e.g., fluoroquinolones, carbapenems)
- Superinfection: Overgrowth of resistant organisms following broad-spectrum antibiotic use (e.g., C. difficile colitis from clindamycin, fluoroquinolones)
Combination Therapy Rationale:
- Broad empiric coverage (unknown pathogen)
- Synergy (e.g., β-lactam + aminoglycoside for Pseudomonas)
- Prevent resistance emergence (e.g., TB — multiple drugs prevent resistant strains)
- Polymicrobial infections (e.g., intra-abdominal infections — multiple organisms)
⚡ Exam Tip for INI CET (AIIMS PG): Bacteriostatic drugs (tetracyclines, macrolides, sulfonamides) may antagonize bactericidal drugs (β-lactams, aminoglycosides) — avoid combining in serious infections. Exception: Trimethoprim-sulfamethoxazole (TMP-SMX) is synergistic despite both being bacteriostatic.