Antimicrobial Chemotherapy
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Antimicrobial Chemotherapy — Key Facts for FMGE Core concept: Antibiotics work by targeting bacterial-specific pathways not present in human cells High-yield point: Bactericidal vs bacteriostatic distinction determines clinical use ⚡ Exam tip: Most common FMGE question pattern: matching antibiotic class with mechanism of action
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Antimicrobial Chemotherapy — FMGE Study Guide
Mechanism of Action
Antimicrobial agents work through several key mechanisms:
1. Inhibition of Cell Wall Synthesis
- Beta-lactams (Penicillins, Cephalosporins, Carbapenems): Bind to penicillin-binding proteins (PBPs), inhibiting transpeptidation → bactericidal
- Vancomycin: Inhibits cell wall synthesis by binding D-Ala-D-Ala terminus of peptidoglycan — used for MRSA
- Bacitracin: Prevents dephosphorylation of bactoprenol
2. Inhibition of Protein Synthesis
- Aminoglycosides (Gentamicin, Streptomycin): Bind 30S ribosomal subunit → mRNA misreading → bactericidal
- Tetracyclines: Bind 30S subunit → block tRNA attachment → bacteriostatic
- Macrolides (Erythromycin, Azithromycin): Bind 50S subunit → block translocation → bacteriostatic
- Chloramphenicol: Binds 50S → blocks peptidyl transferase → bacteriostatic
3. Inhibition of Nucleic Acid Synthesis
- Quinolones (Ciprofloxacin, Levofloxacin): Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV → bactericidal
- Rifampicin: Inhibits DNA-dependent RNA polymerase → bactericidal (used in TB)
- Metronidazole: Generated free radicals damage DNA → bactericidal (anaerobes)
4. Inhibition of Folic Acid Synthesis
- Sulfonamides: Compete with PABA for dihydropteroate synthase (bacteriostatic)
- Trimethoprim: Inhibits dihydrofolate reductase — often combined with sulfamethoxazole (SMX-TMP)
5. Disruption of Cell Membrane Integrity
- Polymyxins (Colistin): Disrupt outer membrane of Gram-negative bacteria
- Daptomycin: Depolarizes cell membrane (Gram-positive only)
Classification of Antibiotics
| Class | Examples | Mechanism | Type |
|---|---|---|---|
| Penicillins | Amoxicillin, Ampicillin | Cell wall inhibition | Bactericidal |
| Cephalosporins | Ceftriaxone, Cefotaxime | Cell wall inhibition | Bactericidal |
| Carbapenems | Meropenem, Imipenem | Cell wall inhibition | Bactericidal |
| Aminoglycosides | Gentamicin, Amikacin | 30S inhibition | Bactericidal |
| Fluoroquinolones | Ciprofloxacin, Levofloxacin | DNA gyrase inhibition | Bactericidal |
| Macrolides | Azithromycin, Erythromycin | 50S inhibition | Bacteriostatic |
Key Pharmacokinetic Principles
- Time-dependent antibiotics: Efficacy depends on duration above MIC (Beta-lactams)
- Concentration-dependent antibiotics: Efficacy depends on peak concentration/MIC ratio (Aminoglycosides, Quinolones)
- Post-antibiotic effect (PAE): Persistent effect after drug levels fall below MIC
Spectrum of Activity
Narrow spectrum: Penicillin G, Vancomycin Broad spectrum: Ceftriaxone, Carbapenems Extended spectrum: Covers Gram-negatives including Pseudomonas
Important patterns for FMGE:
- Gram-positive cocci → Vancomycin, Linezolid
- Gram-negative rods → Ceftriaxone, Ciprofloxacin
- Anaerobes → Metronidazole, Clindamycin
- Pseudomonas → Piperacillin-tazobactam, Ceftazidime
Resistance Mechanisms
- Enzyme inactivation: Beta-lactamases destroy beta-lactam ring (plasmid-mediated TEM, SHV enzymes)
- Altered target site: MRSA has altered PBP (mecA gene)
- Decreased permeability: Gram-negative outer membrane barrier
- Active efflux: Efflux pumps remove drug from cell
- Bypass of pathway: Alternative folate synthesis
Combination Therapy
Justified in:
- Serious infections with unknown pathogen (empiric therapy)
- Polymicrobial infections (intra-abdominal)
- To prevent emergence of resistance (TB treatment)
- Synergy (Gentamicin + Penicillin for Enterococcus)
Essential Points for FMGE
- Bactericidal: Beta-lactams, Aminoglycosides, Quinolones, Metronidazole, Vancomycin
- Bacteriostatic: Tetracyclines, Macrolides, Chloramphenicol, Clindamycin, Sulfonamides
- Higher MIC in presence of competitive substrate (important for sulfa drugs)
- Remember: CSF penetration requires lipophilic drugs or inflamed meninges
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