Pharmacology and Pharmacokinetics/Pharmacodynamics of Antimicrobial Agents
Core concepts
Understand time-dependent vs. concentration-dependent killing and the pharmacodynamic indices that predict efficacy: fT>MIC (beta-lactams), Cmax/MIC (aminoglycosides), and AUC/MIC (vancomycin, fluoroquinolones, azithromycin). Know the four pharmacokinetic parameters (absorption, distribution, metabolism, excretion) and how they shift in obesity, critical illness, renal/hepatic dysfunction, and augmented renal clearance. Understand protein binding and its effect on free drug, volume of distribution, and half-life. Recognize post-antibiotic effect (PAE) differences (aminoglycosides, fluoroquinolones have PAE; beta-lactams generally do not). Know mechanisms of resistance in pharmacologic terms: beta-lactamases (including ESBL, AmpC, carbapenemases), efflux pumps, porin loss, and target modification.
Traps
- Confusing MIC (a static measure) with the pharmacodynamic target (a dynamic exposure index).
- Assuming higher dose always improves outcomes; for concentration-dependent drugs, toxicity may rise before efficacy.
- Ignoring free (unbound) drug fraction when protein binding is high.
- Applying standard dosing in augmented renal clearance or CRRT without adjustment.
Rule of thumb
When efficacy depends on time above MIC, optimize frequency and infusion strategy; when it depends on peak or AUC, optimize total exposure and monitor for toxicity.
Worked example: A beta-lactam with a short half-life and time-dependent killing: extending infusion (prolonged or continuous) raises fT>MIC and improves target attainment without increasing total daily dose.