Antimicrobial Pharmacology Principles
Antimicrobial pharmacology bridges drug mechanisms, pharmacokinetics, and microbial biology to guide rational antibiotic selection and dosing.
## 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:
1. **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.
2. **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).
3. **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