Clinical applications of population pharmacokinetic models of antibiotics: Challenges and perspectives.

Because of increasing antimicrobial resistance and the shortage of new antibiotics, there is a growing need to optimize the use of old and new antibiotics. Modelling of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of antibiotics can support the optimization of dosing regimens. Antimicrobial efficacy is determined by susceptibility of the drug to the microorganism and exposure to the drug, which relies on the PK and the dose. Population PK models describe relationships between patients characteristics and drug exposure. This article highlights three clinical applications of these models applied to antibiotics: 1) dosing evaluation of old antibiotics, 2) setting clinical breakpoints and 3) dosing individualization using therapeutic drug monitoring (TDM). For each clinical application, challenges regarding interpretation are discussed. An important challenge is to improve the understanding of the interpretation of modelling results for good implementation of the dosing recommendations, clinical breakpoints and TDM advices. Therefore, also background information on PK/PD principles and approaches to analyse PK/PD data are provided.