Pharmacodynamics of antimicrobial drugs

Abstract

The importance of pharmacodynamic factors in developing optimal treatment strategies has been confirmed in many studies in in vitro models and in models of infection in experimental animals that simulate human infections, and in clinical studies. The requirement for bactericidal therapy for endocarditis and meningitis, for synergistic combinations to treat enterococcal endocarditis or to shorten the course of antimicrobial therapy, for obtaining Cmax/MIC ratios that are greater than 10 or AUC:MIC ratios that are greater than 100 to 125 for concentration-dependent agents against gram-negative bacilli and 25 to 30 against S pneumoniae, and for percent of time above the MIC that is at least 40% to 50% of the dosing interval for time-dependent agents are a few important pharmacodynamic concepts demonstrated in animal models that have successfully guided therapy of human infections. Pharmacodynamics can also optimize dosing to prevent emergence of resistance and be used to rationalize determination of antimicrobial susceptibility.