Antifungal pharmacokinetics and pharmacodynamics: understanding the implications for antifungal drug resistance

Abstract

Pharmacodynamics (PDs) describe the relationship between drug exposure and outcome. The drug exposures in these analyses are most commonly expressed in a variety of pharmacokinetic terms. The outcome of interest with anti-infective therapy is either microbiologic resolution or a clinical surrogate of treatment efficacy. An in vitro measure of drug potency, such as the minimum inhibitory concentration (MIC) is also frequently considered in this relationship. Examination of the relationships among drug pharmacokinetics, MIC, and efficacy has provided a framework for choice of antifungal drug and dose. These analyses provide a PD target for drug class/organism combinations. The PD target can be useful for defining the upper MIC limit for a drug-dosing regimen that would be expected to result in treatment efficacy. The PD target can be used to optimize dosing regimens and to aid in defining susceptibility breakpoints.