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. 2024 Nov 6;68(11):e0116424.
doi: 10.1128/aac.01164-24. Epub 2024 Oct 21.

Mechanisms leading to in vivo ceftazidime/avibactam resistance development during treatment of GES-5-producing Pseudomonas aeruginosa infections

Cristhian Herrera #  1 , Maria A Gomis-Font #  2 , Carla López-Causapé  2 , María Díez-Aguilar  1 , Pablo A Fraile-Ribot  2 , Laura M Cardeñoso  1 , Antonio Oliver  2
Affiliations

Mechanisms leading to in vivo ceftazidime/avibactam resistance development during treatment of GES-5-producing Pseudomonas aeruginosa infections

Cristhian Herrera et al. Antimicrob Agents Chemother. .

Abstract

The mechanisms underlying ceftazidime/avibactam resistance development in four ceftazidime/avibactam susceptible/resistant pairs of GES-5-producing ST235 Pseudomonas aeruginosa clinical isolates were investigated. In three of the cases, ceftazidime/avibactam resistance was driven by a single mutation leading to GES-27 (P162Q), GES-29 (P162A), or the novel GES-60 (N136S), as confirmed through cloning experiments. Moreover, these mutations were associated with increased cefiderocol MICs but reduced carbapenem, particularly imipenem/relebactam, resistance. Understanding the complexity of resistance mechanisms to the growing repertoire of antipseudomonal β-lactams is crucial to guide optimized treatments and antimicrobial stewardship measures.

Keywords: GES; Pseudomonas aeruginosa; ceftazidime/avibactam.

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Conflict of interest statement

The authors declare no conflict of interest.

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