Journal
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume 43, Issue 4, Pages 370-374Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2013.12.010
Keywords
Lipopeptides; Polymyxins; Synergy
Funding
- Gilead
- Pfizer
- Schering-Plough
- Aventis
- Eli Lilly
- MSD
- Janssen-Cilag
- Astellas
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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 x 10(5) CFU/mL and subinhibitory concentrations of each antibiotic alone or in combination subcultured at 0, 5 and 24 h for colony counting. Synergy was defined as >= 2 log(10) CFU/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 5 h and 24 h, respectively. No antagonism was detected. Colistin alone was bactericidal against two colistin-susceptible isolates at 24 h, whereas the combination was bactericidal against 9 colistin-susceptible isolates at 24 h. 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. (C) 2014 Published by Elsevier B.V.
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