Introduction to pharmacodynamics

Abstract

Since the early appreciation of differences in the time course of antimicrobial activity, much has been learned about the pharmacodynamics of antimicrobials. Specific PK/PD indices have been identified which are of major importance for efficacy and for the prevention of the emergence of resistance. Of major importance, the magnitudes of these PK/PD indices for efficacy have been shown to be very similar in animal infection models and human infections. Modeling has also identified that there are few differences in the index magnitude with different dosing intervals, among drugs within the same antimicrobial class (providing free drug concentrations are used), with different infection sites (except occasionally for pneumonia), and among susceptible and resistant strains of the same type of bacteria. Addition studies have shown that the magnitude of indices can increase significantly with a higher inoculum for S. aureus and that neutrophils have a minor enhancing effect on antimicrobial activity against Enterobacteriaceae but a more variable enhancing effect on activity against S. pneumonia for different antimicrobials. Pharmacodynamic modeling has many applications including establishing new optimal dosing regimens, developing new antimicrobials and formulations, determining susceptibility breakpoints, providing guidelines for empiric therapy, and formulary development.