Emergence of Resistance to Novel Cephalosporin-β-Lactamase Inhibitor Combinations Through the Modification of the Pseudomonas Aeruginosa MexCD-OprJ Efflux Pump

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2021 Jun 1

PMID 34060900

Citations 26

Authors

Maria A Gomis-Font

Cristina Pitart

Ester Del Barrio-Tofino

Yuliya Zboromyrska

Sara Cortes-Lara

Xavier Mulet

Francesc Marco

Jordi Vila

Carla Lopez-Causape

Antonio Oliver

Affiliations

Soon will be listed here.

Abstract

A ceftolozane-tazobactam- and ceftazime-avibactam-resistant Pseudomonas aeruginosa isolate was recovered after treatment (including azithromycin, meropenem, and ceftolozane-tazobactam) from a patient that had developed ventilator-associated pneumonia after COVID-19 infection. Whole-genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux pump MexCD-OprJ), and two missense mutations (Q178R and S133G) located within the first large periplasmic loop of MexD. Through the construction of mutants and complementation assays with wild-type , it was evidenced that resistance to the novel cephalosporin-β-lactamase inhibitor combinations was caused by the modification of MexD substrate specificity.

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