Addressing carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa: the potential of cefiderocol and ceftazidime/avibactam plus aztreonam therapy

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• dc.contributor.author Montero, Maria Milagro
• dc.contributor.author Domene Ochoa, Sandra
• dc.contributor.author Prim, Núria
• dc.contributor.author Ferola, Eliana
• dc.contributor.author López-Causapé, Carla
• dc.contributor.author Gomis-Font, Marian
• dc.contributor.author Ampuero Morisaki, Mario F.
• dc.contributor.author Echeverría Esnal, Daniel
• dc.contributor.author Sorli Redó, M. Luisa
• dc.contributor.author Luque, Sonia
• dc.contributor.author Padilla, Eduardo
• dc.contributor.author Grau Cerrato, Santiago
• dc.contributor.author Oliver, Antonio
• dc.contributor.author Horcajada Gallego, Juan Pablo
• dc.date.accessioned 2025-03-18T07:46:52Z
• dc.date.available 2025-03-18T07:46:52Z
• dc.date.issued 2025
• dc.description Data de publicació electrònica: 18-02-2025
• dc.description.abstract This 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Montero 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/s10096-025-05061-4
• dc.identifier.doi http://dx.doi.org/10.1007/s10096-025-05061-4
• dc.identifier.issn 0934-9723
• dc.identifier.uri http://hdl.handle.net/10230/69963
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Eur J Clin Microbiol Infect Dis. 2025 Feb 18
• dc.rights © 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/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Pseudomonas aeruginosa
• dc.subject.keyword Aztreonam
• dc.subject.keyword Cefiderocol
• dc.subject.keyword Ceftazidime/avibactam
• dc.subject.keyword Chemostat
• dc.subject.keyword PK/PD
• dc.title Addressing carbapenemase-producing extensively drug-resistant Pseudomonas aeruginosa: the potential of cefiderocol and ceftazidime/avibactam plus aztreonam therapy
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion