Synergistic efficacy of ceftazidime/avibactam and aztreonam against carbapenemase-producing Pseudomonas aeruginosa: insights from the hollow-fiber infection model

Montero, Maria Milagro; Domene Ochoa, Sandra; Prim, Núria; Ferola, Eliana; López-Causapé, Carla; Echeverría Esnal, Daniel; Ampuero Morisaki, Mario F.; Vega Toribio, Victoria; Sorli Redó, M. Luisa; Luque Pardos, Sònia; Padilla, Eduardo; Oliver, Antonio; Horcajada Gallego, Juan Pablo

doi:http://dx.doi.org/10.1080/23744235.2024.2396882

Synergistic efficacy of ceftazidime/avibactam and aztreonam against carbapenemase-producing Pseudomonas aeruginosa: insights from the hollow-fiber infection model

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Montero 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). 2025 Jan;57(1):81-8. DOI: 10.1080/23744235.2024.2396882

Abstract

Background: 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.