Antibiotics: A Medical Student's Guide

1. Key Terminology

2. Classification by Mechanism of Action

A. Cell Wall Synthesis Inhibitors

Beta-Lactams

Glycopeptides

• Vancomycin - gram-positive coverage including MRSA
• Teicoplanin - similar spectrum, long half-life (45-70 hrs), IM/IV use

Others in this class

• Daptomycin - cyclic lipopeptide; disrupts cell membrane (gram-positives, MRSA, VRE)
• Bacitracin - topical; blocks lipid carrier in cell wall synthesis
• Isoniazid, ethambutol, cycloserine - target mycobacterial cell wall components

B. Protein Synthesis Inhibitors

• 30S: B = beta-lactams (indirectly), A = Aminoglycosides, T = Tetracyclines
• 50S: C = Chloramphenicol, E = Erythromycin (macrolides), L = Lincosamides (clindamycin), S = Streptogramins

C. DNA / Nucleic Acid Synthesis Inhibitors

3. Types of Antimicrobial Therapy

1. Empiric (Presumptive) - Started before culture results, based on likely pathogens and local resistance patterns. The clinical syndrome should be defined as accurately as possible; severity and comorbidities inform whether to use broad or narrow coverage.
2. Targeted (Precise) - Narrowed to specific organism(s) once culture and sensitivity results return (usually 48-72 hrs). De-escalation - switching to a narrower-spectrum agent once the pathogen is identified - is preferred. Broad unnecessary coverage predisposes to colonization by drug-resistant organisms and C. difficile colitis.
3. Prophylactic (Preventive) - Given before procedures or in defined high-risk settings. Most effective when administered within 1 hour of a planned invasive procedure.

4. Antibiotic Resistance

Four Main Mechanisms of Resistance

1. Limiting uptake - Altered porin proteins in gram-negative outer membranes reduce drug entry (important for beta-lactams in Pseudomonas)
2. Target modification - Altered PBPs (e.g., MRSA's PBP2a encoded by mecA gene) don't bind beta-lactams; ribosomal methylation (ermB gene) confers macrolide resistance in pneumococci
3. Enzymatic inactivation - Beta-lactamases hydrolyze the beta-lactam ring. Over 200 types are known:
   • Class A: Penicillinases (TEM-1, SHV-1); mutations create ESBLs that inactivate all penicillins + cephalosporins
   • KPC (Klebsiella Pneumoniae Carbapenemase): Serine carbapenemase - confers resistance to ALL beta-lactams; treat with ceftazidime-avibactam or meropenem-vaborbactam
   • MBL (Metallo-beta-lactamases): Require zinc; resistant to avibactam (use aztreonam combinations)
4. Active efflux - Membrane pumps export drugs before they reach their target; major mechanism in Pseudomonas and for macrolide resistance (mefA gene in pneumococcus)

Key Resistant Organisms to Know

5. Antibiotic Stewardship

• Improve patient outcomes
• Reduce adverse effects (C. diff, nephrotoxicity, drug reactions)
• Slow the emergence and spread of resistance

• Use the narrowest-spectrum effective agent
• De-escalate when cultures return
• Prescribe correct dose and duration
• Avoid antibiotics for viral infections
• Check local susceptibility patterns (antibiograms)

6. Quick Clinical Recall Summary

MECHANISM
├── Cell Wall       → β-lactams, vancomycin, daptomycin
├── 30S Ribosome    → Aminoglycosides, Tetracyclines
├── 50S Ribosome    → Macrolides, Clindamycin, Chloramphenicol, Linezolid
├── DNA gyrase      → Fluoroquinolones
├── Folate pathway  → Sulfonamides, Trimethoprim
└── RNA polymerase  → Rifampin

BACTERICIDAL: β-lactams, Aminoglycosides, Fluoroquinolones, Vancomycin, Metronidazole
BACTERIOSTATIC: Tetracyclines, Macrolides, Clindamycin, Linezolid, Sulfonamides

• Medical Microbiology 9e - Mechanisms of action, resistance, Table 17.1
• Harrison's Principles of Internal Medicine 22e (2025) - Resistance, pneumococcal susceptibility breakpoints
• Textbook of Family Medicine 9e - Empiric/targeted/prophylactic therapy, Table 15-2
• Current Surgical Therapy 14e - MRSA, beta-lactamase classification, resistant organisms
• Goodman & Gilman's Pharmacological Basis of Therapeutics - Glycopeptides
• Katzung's Basic and Clinical Pharmacology 16e - Teicoplanin