Mechanisms leading to in vivo ceftazidime/avibactam resistance development during treatment of GES-5-producing Pseudomonas aeruginosa infections.
Herrera C; Gomis-Font MA; López-Causapé C; Díez-Aguilar M; Fraile-Ribot PA; Cardeñoso LM; Oliver A
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. Antimicrobial agents and chemotherapy: 2024 doi: 10.1128/aac.01164-24 https://pubmed.ncbi.nlm.nih.gov/39431817