Synergistic effect of fosfomycin and colistin against KPC-producing Klebsiella pneumoniae: pharmacokinetics-pharmacodynamics combined with transcriptomic approach.

ABSTRACT:

Objectives

The aim of this study was to identify the synergistic effect and mechanisms of fosfomycin (FM) combined with colistin (COL) against KPC-producing Klebsiella pneumoniae (KPC-Kp).

Methods

The bactericidal effects, induced drug resistance and cytotoxicity of FM combined with COL were evaluated by time-kill assays and mutation rate test. Time-kill assays and transcriptomics analysis were used to further clarify the mechanism of FM combined with COL. The bacteria were taken from different points in time-kill assays, reactive oxygen species (ROS), nitric oxide and redox related enzymes were detected. The mechanism of synergistic bactericidal action was analyzed by transcriptome.

Results

The bactericidal effect of FM combined with COL was better than that of monot

SUBMITTER: Zhang J 

PROVIDER: S-EPMC11515340 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature