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.This study was carried out as part of our routine work. Authors from the Institute of Biomedicine of Seville, Seville, Spain, are supported by Plan Nacional de I + D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009)—co-financed by European Development Regional Fund A way to achieve Europe, Operative programme Intelligent Growth 2014–2020. T.C.C. is supported by the V Plan Propio of the University of Seville (USE-19631-N). M.E.P.I. is supported by the programme ‘Nicolás Monardes’ (C1-0038–2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain.Peer reviewe