Montero MM; Domene-Ochoa S; Prim N; Ferola E; López-Causapé C; Echeverria D; Morisaki MFA; Vega-Toribio V; Sorlí L; Luque S; Padilla E; Oliver A; Horcajada JP

Abstract: 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. 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. 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. 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. Infectious diseases (London, England): 2025 doi: 10.1080/23744235.2024.2396882 https://pubmed.ncbi.nlm.nih.gov/39212630