title: 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.
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: younghaifei@gmail.com.
authors.forename: Haifei
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Hu
authors.affiliation: Institute of Bacterium Resistance, Anhui Medical University, Hefei, China; Anhui Center for Surveillance of Bacterial Resistance, Hefei, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Clinical Medicine, Xiangya School of Medicine, Central South University, Changsha, China.
authors.forename: Hongru
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Bacterium Resistance, Anhui Medical University, Hefei, China; Anhui Center for Surveillance of Bacterial Resistance, Hefei, China. Electronic address: yeying2@139.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Bacterium Resistance, Anhui Medical University, Hefei, China; Anhui Center for Surveillance of Bacterial Resistance, Hefei, China; Department of Infectious Diseases, Chaohu Hospital of Anhui Medical University, Hefei, China. Electronic address: lijiabin948@vip.sohu.com.
authors.forename: Jiabin
authors.initials: J
authors.lastname: Li
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000302:isolation & purification*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003091:Colistin / Q000008:administration & dosage / Q000627:therapeutic use*; D017576:Daptomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007915:Lepidoptera
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin; D003091:Colistin
keywords: Antimicrobial synergy; Daptomycin; Invertebrate model; Polymyxins