Synergistic efficacy of ceftazidime/avibactam and aztreonam against carbapenemase-producing Pseudomonas aeruginosa : insights from the hollow-fiber infection model
Year: 2024
Type: article
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 isolatesMethods 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.
Institutions: Universitat Pompeu Fabra, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red, Hospital Del Mar, Hospital del Mar Research Institute, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Generalitat de Catalunya, Health Research Institute of the Balearic Islands, Hospital Universitario Son Espases, Hospital Universitario Ramón y Cajal
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: hybrid
Awards: G1694499074, Evaluación in vitro de la apotransferrina como terapia innovadora en las infecciones por Pseudomonas aeruginosa extremadamente resistente mediante un modelo dinámico PK/PD., G2567209517, G5638698898, G5953954702, G6182431501, Impacto clínico y microbiológico de los nuevos antipseudomónicos ceftolozano-tazobactam y Ceftazidima avibactam en la infecciones por Pseudomonas aeruginosa extremadamente resistente en España: Pronostico, Seguridad y seleccion de mutantes resistentes
OpenAlex ID: W4402047289