Integration of pharmacokinetic/pharmacodynamic modeling and simulation in the development of new anti-infective agents - minimum inhibitory concentration versus time-kill curves

The selection of appropriate doses and dosing regimens is extremely important in antimicrobial therapy in order to increase the chances of clinical success and decrease the likelihood of toxic side effects and the development of resistance. Therefore, empirical treatment of bacterial infections is not reliable enough and more rational approaches are needed. Pharmacokinetic/pharmacodynamic (PK/PD) modeling provides a powerful tool to systematically link PK and PD properties in order to predict antimicrobial efficacy. However, commonly used minimum inhibitory concentration (MIC) based PK/PD indices, although easy to obtain, have a number of limitations. Thus, more reliable PK/PD indices need to be developed. The following article provides an overview of the present PK/PD approaches used in anti-infective therapy and discusses their role in improving drug therapy.