1. Synergistic efficacy of ceftazidime/avibactam and aztreonam against carbapenemase-producing <italic>Pseudomonas aeruginosa</italic>: insights from the hollow-fiber infection model.
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Montero, María M., Domene-Ochoa, Sandra, Prim, Núria, Ferola, Eliana, López-Causapé, Carla, Echeverria, Daniel, Morisaki, Mario F. Ampuero, Vega-Toribio, Victoria, Sorlí, Luisa, Luque, Sonia, Padilla, Eduardo, Oliver, Antonio, and Horcajada, Juan P.
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NOSOCOMIAL infections , *AZTREONAM , *PSEUDOMONAS aeruginosa , *CEFTAZIDIME , *KLEBSIELLA infections - Abstract
AbstractBackgroundMethodsResultsConclusionCombination 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) - producingEnterobacterales. However, data about that combination against SBL- and MBL-producingP. aeruginosa are scarce. The objective of the study was to assess thein vitro activity of CZA and aztreonam alone and in combination against SBL- and MBL-producing XDRP. aeruginosa isolatesThe combination was analyzed by means of the hollow-fiber infection model in three selected carbapenemase-producingP. 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 thein vitro efficacy against XDRP. 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 XDRP. aeruginosa , especially in scenarios where no other treatment options are available. [ABSTRACT FROM AUTHOR]- Published
- 2024
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