In Vitro Pharmacodynamic Models to Evaluate Anti-infective Pharmacodynamics

Abstract

In vitro models have provided valuable insight into the pharmacodynamics of antimicrobials and have improved treatment approaches for patients. The use of in vitro models continues to help guide dosing decision for new antimicrobials and reevaluate those used already in clinical practice as resistance emerges. The design of in vitro PD models has not changed significantly since their introduction, but historically the models have been unique to individual laboratories with different methods scattered throughout the literature. The basic principle of the in vitro PK/PD model is to allow for assessment of antimicrobial activity under dynamic exposure conditions. This chapter presents the materials and methods for four different in vitro model types that have been used consistently in the literature to assess antimicrobial PK/PD for a given scenario: one-compartment model, hollow fiber model, biofilm model, and combination therapy model. In addition, this information is supplemented with information to design dosing schemes for the models as well as assess the PD outcomes of the antibiotic simulation. This information provides the basics for in vitro dynamic assessment, and the models can be customized from the presented method to address a specific research question or clinical situation.