Montero, Maria MilagroDomene Ochoa, SandraPrim, NúriaFerola, ElianaLópez-Causapé, CarlaGomis-Font, MarianAmpuero Morisaki, Mario F.Echeverría Esnal, DanielSorli Redó, M. LuisaLuque, SoniaPadilla, EduardoGrau Cerrato, SantiagoOliver, AntonioHorcajada Gallego, Juan Pablo2025-03-182025-03-182025Montero MM, Domene-Ochoa S, Prim N, Ferola E, López-Causapé C, Gomis-Font M, et al. Addressing carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa: the potential of cefiderocol and ceftazidime/avibactam plus aztreonam therapy. Eur J Clin Microbiol Infect Dis. 2025 Feb 18. DOI: 10.1007/s10096-025-05061-40934-9723http://hdl.handle.net/10230/69963Data de publicació electrònica: 18-02-2025This study evaluated the activity of cefiderocol and the combination of ceftazidime/avibactam (CZA) plus aztreonam against carbapenemase-producing extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates. Nine clinical XDR P. aeruginosa isolates with different sequence types and class A (GES) or B (VIM, IMP or NDM) carbapenemases were analysed. Time-kill assays assessed bacterial load reduction for each treatment, while chemostat experiments on four isolates validated these findings. All isolates showed resistance to CZA, with four also resistant to aztreonam. Seven isolates were susceptible to cefiderocol, but two displayed borderline susceptibility (MIC 2-4 mg/L). Time-kill assays demonstrated bactericidal activity by cefiderocol in six isolates at 24 h, while CZA plus aztreonam showed bactericidal effects in three isolates and synergistic/additive effects in four isolates. In the chemostat model, cefiderocol and CZA plus aztreonam were bactericidal in all four tested isolates, with cefiderocol showing greater bacterial reduction in three of these isolates. Both cefiderocol and CZA plus aztreonam achieved significant reductions in bacterial counts compared to controls, but there was no significant difference between cefiderocol monotherapy and the combination. Both cefiderocol and CZA plus aztreonam demonstrated activity against XDR P. aeruginosa carrying metallo-β-lactamase (MBL) and/or serine-β-lactamase (SBL) carbapenemases. Cefiderocol was the only consistently effective monotherapy with a bactericidal effect across all tested isolates in the chemostat model.application/pdfeng© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1007/s10096-025-05061-4Pseudomonas aeruginosaAztreonamCefiderocolCeftazidime/avibactamChemostatPK/PDinfo:eu-repo/semantics/openAccess