Integration of individual preclinical and clinical anti-infective PKPD data to predict clinical study outcomes.

ABSTRACT: The AIDA randomized clinical trial found no significant difference in clinical failure or survival between colistin monotherapy and colistin-meropenem combination therapy in carbapenem-resistant Gram-negative infections. The aim of this reverse translational study was to integrate all individual preclinical and clinical pharmacokinetic-pharmacodynamic (PKPD) data from the AIDA trial in a pharmacometric framework to explore whether individualized predictions of bacterial burden were associated with the trial outcomes. The compiled dataset included for each of the 207 patients was (i) information on the infecting Acinetobacter baumannii isolate (minimum inhibitory concentration, checkerboard assay data, and fitness in a murine model), (ii) colistin plasma concentrations and colistin and mero

SUBMITTER: Aranzana-Climent V 

PROVIDER: S-EPMC11217551 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature