Carbapenem-resistant Gram-negative bacteria exhibiting clinically undetected cefiderocol heteroresistance leads to treatment failure in a murine model of infection.

ABSTRACT:

Introduction

Carbapenem-resistant (CR) Gram-negative pathogens are classified by the WHO as critical threats due to limited therapeutic options. Cefiderocol (CFD), a novel siderophore cephalosporin, shows promise but remains unapproved in China. This study investigated the prevalence, clinical impact, and genetic mechanisms of cefiderocol heteroresistance (CFD-HR) in CR and ESBL-producing clinical isolates from China, where CFD remains unapproved.

Methods

A total of 407 CR and ESBL-producing isolates were analyzed. CFD-HR was identified by population analysis profiles (PAPs). Clinical relevance was assessed through disk diffusion susceptibility testing, time-kill assays, and a murine peritonitis model. Genetic mechanisms and stability were elucidated by whole-genome sequenci

SUBMITTER: Liu H 

PROVIDER: S-EPMC12098276 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature