Antimicrobial Pharmacology Principles

Overview

Rational antimicrobial therapy requires understanding the relationship between drug pharmacokinetics (PK — how the body handles the drug), pharmacodynamics (PD — how the drug affects the microorganism), and microbial susceptibility (MIC). These principles guide drug selection, dosing, and duration to maximize efficacy and minimize resistance development.

Bactericidal vs Bacteriostatic

Bactericidal drugs kill >99.9% of bacteria; bacteriostatic drugs inhibit growth without direct killing, relying on host immunity for elimination. Bactericidal agents include beta-lactams, aminoglycosides, fluoroquinolones, and vancomycin. Bacteriostatic agents include tetracyclines, macrolides, sulfonamides, and clindamycin. Clinical relevance: bactericidal drugs are preferred for infective endocarditis, meningitis, and immunocompromised patients where host defense is impaired.

PK/PD Relationships

Three PK/PD indices predict antimicrobial efficacy:

Time-dependent killing (T>MIC): Efficacy correlates with the percentage of the dosing interval that free drug concentrations exceed the MIC. Beta-lactams and vancomycin. Optimize by extending infusion time or increasing dose frequency.
Concentration-dependent killing (Cmax/MIC): Efficacy correlates with peak concentration relative to MIC. Aminoglycosides and fluoroquinolones. Optimize by giving high doses less frequently (once-daily aminoglycosides).
AUC/MIC: Efficacy correlates with total drug exposure relative to MIC. Fluoroquinolones (AUC/MIC >125 for gram-negative; >30-50 for gram-positive), vancomycin (AUC/MIC 400-600).

Minimum Inhibitory Concentration (MIC)

MIC is the lowest drug concentration that inhibits visible bacterial growth after 18-24 hours. Clinical breakpoints (S/I/R) are established by CLSI/EUCAST based on pharmacokinetics and outcome data. Post-antibiotic effect (PAE) describes continued suppression of bacterial growth after drug removal, relevant for aminoglycosides and fluoroquinolones.

Empiric vs Targeted Therapy

Empiric therapy covers likely pathogens based on infection site and local epidemiology before culture results. De-escalation to targeted, narrower-spectrum therapy once susceptibility data are available reduces resistance selection pressure and side effects.

Key Takeaways

PK/PD parameters (T>MIC, Cmax/MIC, AUC/MIC) determine optimal dosing strategies for each drug class
Beta-lactams are time-dependent; aminoglycosides and fluoroquinolones are concentration-dependent
MIC breakpoints define susceptibility; de-escalation based on culture results reduces resistance pressure
Bactericidal drugs are preferred in immunocompromised hosts and high-stakes infections