Model-informed dose optimisation of polymyxin-rifampicin combination therapy against multidrug-resistant Acinetobacter baumannii.

ABSTRACT:

Objectives

Antimicrobial resistance is a major global threat. Because of the stagnant antibiotic pipeline, synergistic antibiotic combination therapy has been proposed to treat rapidly emerging multidrug-resistant (MDR) pathogens. We investigated antimicrobial synergy of polymyxin/rifampicin combination against MDR Acinetobacter baumannii.

Methods

In vitro static time-kill studies were performed over 48 h at an initial inoculum of ∼10⁷ CFU/mL against three polymyxin-susceptible but MDR A. baumannii isolates. Membrane integrity was examined at 1 and 4 h post-treatment to elucidate the mechanism of synergy. Finally, a semi-mechanistic PK/PD model was developed to simultaneously describe the time course of bacterial killing and prevention of regrowth by mono- and com

SUBMITTER: Zhao J 

PROVIDER: S-EPMC11608097 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature