Montero, Maria MilagroDomene Ochoa, SandraPrim, NúriaFerola, ElianaLópez-Causapé, CarlaEcheverría Esnal, DanielAmpuero Morisaki, Mario F.Vega Toribio, VictoriaSorlí, LuisaLuque Pardos, SòniaPadilla, EduardoOliver, AntonioHorcajada Gallego, Juan Pablo2024-11-132024-11-132024Montero MM, Domene-Ochoa S, Prim N, Ferola E, López-Causapé C, Echeverria D, et al. Synergistic efficacy of ceftazidime/avibactam and aztreonam against carbapenemase-producing Pseudomonas aeruginosa: insights from the hollow-fiber infection model. Infect Dis (Lond). 2024 Aug 30:1-8. DOI: 10.1080/23744235.2024.23968822374-4235http://hdl.handle.net/10230/68506Data de publicació electrònica: 30-08-2024Background: Combination therapy is an attractive therapeutic option for extensively drug-resistant (XDR) Pseudomonas aeruginosa infections. Existing data support the combination of aztreonam and ceftazidime/avibactam (CZA) against class serine-β-lactamase (SBL)- and metallo-β-lactamase (MBL) - producing Enterobacterales. However, data about that combination against SBL- and MBL-producing P. aeruginosa are scarce. The objective of the study was to assess the in vitro activity of CZA and aztreonam alone and in combination against SBL- and MBL-producing XDR P. aeruginosa isolates. Methods: The combination was analyzed by means of the hollow-fiber infection model in three selected carbapenemase-producing P. aeruginosa isolates that were representative of the three most common XDRP. aeruginosa high-risk clones (ST175, ST111, ST235) responsible for global nosocomial infection outbreaks. Results: The three isolates were nonsusceptible to CZA and nonsusceptible to aztreonam. In the dynamic hollow-fiber infection model, the combination of CZA plus aztreonam exerts a bactericidal effect on the isolates, regardless of their resistance mechanism and demonstrates synergistic interactions against three isolates, achieving a bacterial reduction of 5.07 log10 CFU/ml, 5.2 log10 CFU/ml and 4 log10 CFU/ml, respectively. Conclusion: The combination of CZA and aztreonam significantly enhanced the in vitro efficacy against XDR P. aeruginosa isolates compared to each monotherapy. This improvement suggests that the combination could serve as a feasible treatment alternative for infections caused by carbapenemase-producing XDR P. aeruginosa, especially in scenarios where no other treatment options are available.application/pdfeng© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1080/23744235.2024.2396882PK/PDPseudomonas aeruginosaAztreonamCeftazidime/avibactamHollow-fiberinfo:eu-repo/semantics/openAccess