Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling.

ABSTRACT: Semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD) modeling is increasingly used for antimicrobial drug development and optimization of dosage regimens, but systematic simulation-estimation studies to distinguish between competing PD models are lacking. This study compared the ability of static and dynamic in vitro infection models to distinguish between models with different resistance mechanisms and support accurate and precise parameter estimation. Monte Carlo simulations (MCS) were performed for models with one susceptible bacterial population without (M1) or with a resting stage (M2), a one population model with adaptive resistance (M5), models with pre-existing susceptible and resistant populations without (M3) or with (M4) inter-conversion, and a model with two pre-existing po

SUBMITTER: Jacobs M 

PROVIDER: S-EPMC4788427 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature