Colistin enhances therapeutic efficacy of daptomycin or teicoplanin in a murine model of multiresistant Acinetobacter baumannii sepsis

•Only few compounds were found to be active against the MDR strain of A. baumannii•Colistin is an amphipatic peptide antibiotic that can be considered a prototype membrane-perturbing agent.•The permeabilizing effect of colistin on the A. baumannii outer membrane may facilitate the entry of glycopeptide and lipopeptide molecules, which are usually excluded due to their size, resulting in an improvement patient outcomes in severe infections due to multiresistant microorganisms such as A. baumannii.

We investigated the efficacy of colistin combined with teicoplanin or daptomycin in an experimental mouse model of multiresistant Acinetobacter baumannii infection. Animal received intraperitoneally 1 ml saline containing 2 × 1010 CFU of A. baumannii. Colistin, daptomycin, teicoplanin, and colistin plus daptomycin or teicoplanin were given by intraperitoneal administration 2 h after bacterial challenge. A control group received sodium chloride solution. In the in vitro study A. baumannii showed to be susceptible only to colistin with MIC of 2 mg/l. In the in vivo study, colistin alone showed a good antimicrobial efficacy. When combined with teicoplanin or daptomycin, colistin produced the lowest bacterial and the best survival rates. In immunological studies, when colistin was associated to daptomycin or teicoplanin, both the number and the cytotoxic activity of NK cells increased. In conclusion, colistin combined with teicoplanin or daptomycin may improve the therapy of multiresistant A. baumannii infection.