Synergistic Effect of Ceftazidime-Avibactam, Imipenem-Relebactam, Meropenem-Varbobactam with Aztreonam, Colistin or Fosfomycin on Metallo-b-lactamase-Producing Klebsiella pneumoniae Strains

Τhe objective of this study was to assess the in vitro synergy between the new antibacterial agents CZA, M/V and I/R combined with aztreonam (AZM), colistin (COL) and fosfomycin (FOS) against MBL producing Klebsiella pneumoniae strains. This was done to identify the most effective combination regimen that could offer alternative treatment options for infections caused by MBL carbapenemase-producing Klebsiella pneumoniae.A total of 169 MBL-producing Klebsiella pneumoniae single clinical isolates (89 NDM, 66 NDM+KPC and 14 VIM) were included in the study, collected between 1 March 2023 and 30 September 2024. Of these, 86 were isolated from urine, 45 from blood, 27 from wound cultures and 11 from bronchoalveolar secretions. the strongest synergistic effects were observed with the combination of AZM plus CZA, MV, and IR, followed by combinations of FOS plus CZA, MV, and IR, suggesting promising therapeutic options for MBL-producing CRKP infections. Additionally, COL-based combinations with CZA, MV, and IR provided a better additive effect, emphasizing the need for tailored therapeutic strategies.