Efficacy of monotherapy and combined antibiotic therapy for carbapenem-resistant Acinetobacter baumannii pneumonia in an immunosuppressed mouse model

Acinetobacter baumannii is an important cause of nosocomial infection with increasing carbapenem resistance. The aim of this study was to compare the efficacy of colistin + rifampicin and imipenem + rifampicin combinations with that of several other antibiotic regimens against carbapenem-resistant A. baumannii pneumonia using an immunosuppressed mouse model. Three different A. baumannii strains with diverse resistance mechanisms (OXA-51-, IMP-1- and VIM-2-type beta-lactamases) were used. Among the monotherapy regimens, only rifampicin significantly reduced the bacterial load in lungs 24 h after infection with the OXA-51-producing strain. Addition of rifampicin to either imipenem or colistin yielded synergistic results after 48 h. Rifampicin was bactericidal against the IMP-1-producing strain, and only the imipenem + rifampicin combination yielded synergistic effects. In contrast, rifampicin alone was not effective against the VIM-2-producing strain, but the imipenem + rifampicin combination was bacteriostatic even at 24 h post-infection. Tigecycline and amikacin were not effective against any of the three strains. Rifampicin-based combinations were effective against A. baumannii bacteraemia and improved survival regardless of the strain type. Contrary to the similar minimum inhibitory concentration results, the antibacterial effects of rifampicin were quite different according to the strains; a tailored antibiotic strategy must be considered in treatment. Addition of rifampicin to either imipenem or colistin would be effective. (C) 2008 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.