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. 2021 Aug 17;65(9):e0098621.
doi: 10.1128/AAC.00986-21. Epub 2021 Aug 17.

In Vivo Evolution of GES β-Lactamases Driven by Ceftazidime/Avibactam Treatment of Pseudomonas aeruginosa Infections

Pablo A Fraile-Ribot  1 , Javier Fernández  2 , María A Gomis-Font  1 , Lorena Forcelledo  3 , Xavier Mulet  1 , Carla López-Causapé  1 , Antonio Oliver  1
Affiliations

In Vivo Evolution of GES β-Lactamases Driven by Ceftazidime/Avibactam Treatment of Pseudomonas aeruginosa Infections

Pablo A Fraile-Ribot et al. Antimicrob Agents Chemother. .

Abstract

The mechanisms underlying an in vivo switch in the resistance phenotype of P. aeruginosa after ceftazidime-avibactam treatment was investigated. The initial isolate (a blood culture) was resistant to meropenem but remained susceptible to antipseudomonal cephalosporins and combinations with β-lactamase inhibitors. One week after ceftazidime-avibactam therapy, a subsequent isolate (a rectal swab) recovered from the same patient showed the opposite phenotype. Whole-genome sequence analysis revealed a single SNP difference between both (ST235) isolates, leading to a P162S change in blaGES-5, creating blaGES-15. Thus, blaGES-1, blaGES-5, and blaGES-15 were cloned and expressed in the wild-type strain PAO1. Susceptibility profiles confirmed the P162S substitution reverted the carbapenemase phenotype determined by the G170S change of GES-5 back into the ESBL phenotype of GES-1.

Keywords: Pseudomonas aeruginosa; beta-lactamase inhibitors; carbapenemases; drug resistance evolution.

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