Efficacy of dual carbapenem treatment in a murine sepsis model of infection due to carbapenemase-producing Acinetobacter baumannii

Objectives: To evaluate the in vivo efficacy of a dual carbapenem combination containing imipenem plus meropenem against carbapenem-resistant Acinetobacter baumannii producing carbapenemases OXA-23 or OXA-58. Methods: An experimental model of peritonitis using C57BL/6J female mice was developed and the minimum Lethal doses were calculated for infections due to OXA-23 or OXA-58 producers of A. baumannii clinical isolates. The efficacies of the carbapenems in monotherapy and in combination were tested. Results: Meropenem was better than imipenem in mice infected with either of the carbapenem-resistant A. baumannii (CRAb) strains. The combination of meropenem plus imipenem significantly improved the clearance of CRAbs from spleen compared with non-treated groups. The carbapenem-containing combination was better than imipenem for treating mice infected with both carbapenemase producers. In blood, the carbapenem combination significantly decreased the bacterial Load of the OXA-23 producers compared with imipenem or meropenem used in monotherapy. Conclusions: These results suggest that dual carbapenem combination could be an option for the treatment of infections due to carbapenemase-producing A. baumannii such as OXA-23 and OXA-58 producers.