Pharmacodynamics in the study of drug resistance and establishing in vitrosusceptibility breakpoints: ready for prime time

Considerable advancements have been made in providing informative, relevant interpretations of the results of antimicrobial susceptibility tests to cl inicians, clinical microbiologists, epidemiologists, and researchers. At th e same time, the science of pharmacokinetics has flourished, and the import ance of drug exposure in vivo on outcome is now recognized by researchers a nd clinicians alike. More recently, pharmacokinetic and quantitative measur es of antimicrobial susceptibility have been integrated using pharmacokinet ic-pharmacodynamic (PK-PD) models to forecast clinical and microbiological outcomes. Stochastic methods utilizing patient population pharmacokinetics, target organism minimum inhibitory concentration (Mlc) distributions, and PK-PD targets from non-clinical models of infection or clinical data have e stablished a new paradigm for determining in vitro susceptibility breakpoin ts and selection of empirical therapy in clinical practice. Given the incre asing problem of antimicrobial resistance, these new tools are valuable add itions for clinicians, researchers, and regulatory authorities.