Pharmacokinetic-pharmacodynamic modelling to investigate in vitro synergy between colistin and fusidic acid against MDR Acinetobacter baumannii.

ABSTRACT:

Objectives

The potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time-kill experiments in order to estimate clinical efficacy.

Methods

For six clinical strains, 312 individual time-kill experiments were performed including 113 unique pathogen-antimicrobial combinations. A wide range of concentrations (0.25-8192 mg/L for colistin and 1-8192 mg/L for fusidic acid) were explored, alone and in combination. PKPD modelling sought to quantify synergistic effects.

Results

A PKPD model confirmed synergy in that colistin EC50 was found to decrease by 83%

SUBMITTER: Phee LM 

PROVIDER: S-EPMC6419616 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature