Characterization of Pseudomonas aeruginosa resistance to ceftolozane-tazobactam due to ampC and/or ampD mutations observed during treatment using semi-mechanistic PKPD modeling.

ABSTRACT: A double ampC (AmpC^G183D) and ampD (AmpD^H157Y) genes mutations have been identified by whole genome sequencing in a Pseudomonas aeruginosa (PaS) that became resistant (PaR) in a patient treated by ceftolozane/tazobactam (C/T). To precisely characterize the respective contributions of these mutations on the decreased susceptibility to C/T and on the parallel increased susceptibility to imipenem (IMI), mutants were generated by homologous recombination in PAO1 reference strain (PAO1- AmpC^G183D, PAO1-AmpD^H157Y, PAO1-AmpC^G183D/AmpD^H157Y) and in PaR (PaR-AmpC^PaS/AmpD^PaS). Sequential time-kill curve experiments were conducted on all strains and analyzed by semi-mechanistic PKPD modeling.

SUBMITTER: Deroche L 

PROVIDER: S-EPMC10583683 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature