title: Colistin/daptomycin: an unconventional antimicrobial combination synergistic in vitro against multidrug-resistant Acinetobacter baumannii.
abstract: The in vitro activity of the combination colistin/daptomycin was evaluated against multidrug-resistant Acinetobacter baumannii clinical isolates. Clonal relationships were assessed by pulsed-field gel electrophoresis. The following synergy studies were undertaken: (i) daptomycin MICs were determined by E-test on Mueller-Hinton agar plates supplemented with a subinhibitory concentration of colistin; and (ii) time-kill methodology using tubes containing an inoculum of 5×10(5)CFU/mL and subinhibitory concentrations of each antibiotic alone or in combination subcultured at 0, 5 and 24h for colony counting. Synergy was defined as ≥2log10CFU/mL decrease of viable colonies compared with colistin alone. Ten colistin-susceptible and four colistin-resistant A. baumannii isolates were tested. Isolates were assigned to nine different clonal types. Enhanced in vitro activity of the combination was detected only against colistin-susceptible isolates; using plates supplemented with colistin, the daptomycin MIC was reduced by 4- to 128-fold. From a total of 30 isolate-concentration combinations in time-kill studies, a synergistic interaction was detected in 16 (53.3%). The combination exhibited synergy against 8 and 12 of these combinations at 5h and 24h, respectively. No antagonism was detected. Colistin alone was bactericidal against two colistin-susceptible isolates at 24h, whereas the combination was bactericidal against 9 colistin-susceptible isolates at 24h. Against all colistin-resistant isolates, the combination exhibited a static effect and indifference in time-kill studies. Potent in vitro synergistic interactions between colistin and daptomycin provide evidence that this unorthodox combination may be beneficial in the treatment of colistin-susceptible multidrug-resistant A. baumannii.
authors.affiliation: 4th Department of Internal Medicine, Athens University School of Medicine, University General Hospital 'Attikon', 1 Rimini Str., Chaidari, 124 62 Athens, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Galani
authors.affiliation: 4th Department of Internal Medicine, Athens University School of Medicine, University General Hospital 'Attikon', 1 Rimini Str., Chaidari, 124 62 Athens, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Orlandou
authors.affiliation: Department of Clinical Microbiology, 'Sotiria' General and Chest Diseases Hospital, 152 Mesogeion Ave., 11527 Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Moraitou
authors.affiliation: 4th Department of Internal Medicine, Athens University School of Medicine, University General Hospital 'Attikon', 1 Rimini Str., Chaidari, 124 62 Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Petrikkos
authors.affiliation: 4th Department of Internal Medicine, Athens University School of Medicine, University General Hospital 'Attikon', 1 Rimini Str., Chaidari, 124 62 Athens, Greece. Electronic address: msouli@med.uoa.gr.
authors.forename: Maria
authors.initials: M
authors.lastname: Souli
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D016521:Electrophoresis, Gel, Pulsed-Field; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases; D017576:Daptomycin; D003091:Colistin
keywords: Lipopeptides; Polymyxins; Synergy