In vivo activity of daptomycin/colistin combination therapy in a Galleria mellonella model of Acinetobacter baumannii infection

Abstract

Antimicrobial treatment of multidrug-resistant Acinetobacter baumannii (MDR-AB) infections continues to pose significant challenges. With limited options, clinicians have been pushed towards using unorthodox combinations of licensed antibiotics. Although daptomycin/colistin combination appears to be a promising treatment option based on in vitro data, further preclinical work is needed. In this study, the A. baumannii–Galleria mellonella system was employed to study the in vivo efficacy of this combination in order to determine whether it should be explored further for the treatment of MDR-AB infections. The antimicrobial activity of colistin alone and in combination with daptomycin was assessed versus an A. baumannii type strain (ATCC 19606) and a MDR-AB clinical strain (GN2231) isolated in Anhui, China. Synergy studies were performed using the microtitre plate chequerboard assay and time–kill methodology. The in vivo activity of daptomycin/colistin combination was assessed using a G. mellonella larvae model. The combination of daptomycin and colistin was bactericidal against both strains tested. In chequerboard assays, daptomycin was highly active against A. baumannii when combined with colistin [fractional inhibitory concentration index (FICI) of <0.5]. Treatment of G. mellonella larvae infected with lethal doses of A. baumannii resulted in significantly enhanced survival rates when daptomycin was given with colistin compared with colistin treatment alone (P<0.05). This work suggests that daptomycin/colistin combination is highly active against A. baumannii both in vitro and in a simple invertebrate model of infection.