Antimicrobial Mechanisms of Action and Susceptibility Testing
Core concepts
Know drug targets: cell wall (beta-lactams, vancomycin), protein synthesis (aminoglycosides, macrolides, tetracyclines, chloramphenicol, clindamycin, linezolid), nucleic acid (fluoroquinolones, rifampin), folate pathway (sulfonamides, trimethoprim), and cell membrane (polymyxins, daptomycin). Understand bactericidal vs bacteriostatic and that this distinction is context-dependent.
Know susceptibility methods: disk diffusion (Kirby-Bauer), broth microdilution (MIC), E-test, and automated systems. Understand breakpoints (CLSI/EUCAST), MIC interpretation, and special tests (ESBL, carbapenemase, MRSA, VRE, inducible clindamycin resistance via D-test). Know mechanisms of resistance: enzymatic (beta-lactamase, carbapenemase), target modification (MRSA mecA, ribosomal methylation), efflux, and reduced permeability.
Traps to expect
- Confusing MIC (lowest concentration inhibiting visible growth) with MBC (lowest concentration killing 99.9%).
- Assuming disk diffusion measures MIC directly - it measures zone size, which is correlated.
- Forgetting that D-test detects inducible clindamycin resistance in erythromycin-resistant staphylococci.
- Overlooking that breakpoints differ by organism and body site.
Worked example / rule of thumb
A S. aureus is erythromycin-resistant and clindamycin-susceptible on disk diffusion. Rule of thumb: perform a D-test - if the clindamycin zone flattens toward the erythromycin disk, report clindamycin as resistant (inducible MLSb resistance). This prevents treatment failure.