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Int J Antimicrob Agents. 2014 Apr;43(4):370-4. doi: 10.1016/j.ijantimicag.2013.12.010. Epub 2014 Feb 4.

Colistin/daptomycin: an unconventional antimicrobial combination synergistic in vitro against multidrug-resistant Acinetobacter baumannii.

Author information

1
4th Department of Internal Medicine, Athens University School of Medicine, University General Hospital 'Attikon', 1 Rimini Str., Chaidari, 124 62 Athens, Greece.
2
Department of Clinical Microbiology, 'Sotiria' General and Chest Diseases Hospital, 152 Mesogeion Ave., 11527 Athens, Greece.
3
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.

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.

KEYWORDS:

Lipopeptides; Polymyxins; Synergy

[Indexed for MEDLINE]

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