Employing pharmacokinetic and pharmacodynamic principles to optimize antimicrobial treatment in the face of emerging resistance

Abstract

Antimicrobial efficacy in vivo is not exclusively defined by the activity of an antibiotic as determined in the in vitro susceptibility test. Knowledge of the pharmacokinetics and pharmacodynamics of antimicrobials and all phenomena occurring between antimicrobial agents and microorganisms is imperative. The pharmacodynamic (PD) parameters most often used in studies of antibiotic effect include the following relationships: the maximum free concentration (fC max) to minimum inhibitory concentration (MIC) ratio, the free area under the curve (fAUC/MIC) ratio and the duration of time the free concentration exceeds the MIC (fT>MIC). Utilization of known pharmacokinetic/ pharmacodynamic surrogate relationships should help to optimize treatment outcome, especially in the face of emerging resistance among Gram-positive and Gramnegative bacteria. Clinical studies in the field of antibacterial PD are still relatively scarce, and much information is needed to enable relevant dosing strategies for all types of antibiotics against all common infections and microorganisms. In this review, the distinctive patterns of antimicrobial activity based on PD parameters are discussed. Various antibiotics and bacterial pathogens can be used as models to demonstrate the utility of PD parameters in predicting the in vivo efficacy of antimicrobial therapy. And finally, the use of computer modeling with Monte Carlo population simulations can further enhance the predictability of antimicrobial efficacy when using PD parameters.