title: In vivo efficacy of telavancin/colistin combination therapy in a Galleria mellonella model of Acinetobacter baumannii infection.
abstract: Treatment of Acinetobacter baumannii infections is challenging owing to widespread multidrug resistance and the lack of novel agents. There is now considerable interest in the potential of unorthodox combination therapies such as colistin and glycopeptides (e.g. vancomycin and teicoplanin), since potent synergy can be demonstrated in vitro. A simple invertebrate model (Galleria mellonella) has been developed to assess the in vivo activity of antimicrobial therapies and was used to investigate the efficacy of colistin combined with the lipoglycopeptide telavancin in the treatment of A. baumannii infection. Galleria mellonella larvae were inoculated with 10⁵ CFU/larvae of A. baumannii type strain ATCC 19606 or the multidrug-resistant clinical isolate AB210. Infected caterpillars were treated with either telavancin (10 mg/kg), colistin (2.5 mg/kg) or a telavancin/colistin combination. Larvae were incubated at 37 °C for up to 96 h and were scored daily. Survival curves were plotted and analysed using the log-rank test. The telavancin/colistin combination was effective in the treatment of larvae infected with both strains but was superior to colistin monotherapy in the treatment of A. baumannii AB210 (P<0.001). The combination of telavancin and colistin was effective in a simple invertebrate model of A. baumannii infection. This is in agreement with a previous in vitro study and provides preliminary in vivo evidence that such a combination might be useful therapeutically.
authors: Antimicrobial Research Group, Centre for Immunology and Infectious Disease, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, 4 Newark Street, London E1 2AT, UK.
authors: Michael
authors: M
authors: Hornsey
authors: Lynette
authors: L
authors: Phee
authors: Christopher
authors: C
authors: Longshaw
authors: David W
authors: DW
authors: Wareham
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000617:Aminoglycosides / Q000008:administration & dosage*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D003091:Colistin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D007814:Larva / Q000382:microbiology; D007915:Lepidoptera / Q000382:microbiology; D000077427:Lipoglycopeptides; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000077427:Lipoglycopeptides; C487637:telavancin; D003091:Colistin