Assessment of the in vitro synergy of daptomycin plus linezolid against multidrug-resistant enterococci

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State: Public
Version: Final published version
Serval ID
serval:BIB_7FC18EAF629F
Type
Article: article from journal or magazin.
Collection
Publications
Title
Assessment of the in vitro synergy of daptomycin plus linezolid against multidrug-resistant enterococci
Journal
Journal of Global Antimicrobial Resistance
Author(s)
Entenza J.M., Giddey M., Vouillamoz J., Moreillon P., Mancini S.
ISSN
2213-7165
Publication state
Published
Issued date
2014
Peer-reviewed
Oui
Volume
2
Number
4
Pages
306-308
Language
english
Abstract
The widespread incidence of enterococci resistant to ampicillin, vancomycin and aminoglycosides, the first-line anti-enterococcal antibiotics, has made the treatment of severe enterococcal infections difficult and alternatives should be explored. We investigated the activity of daptomycin combined with linezolid against three Enterococcus faecalis and four Enterococcus faecium strains resistant to standard drugs used for therapy. Minimum inhibitory concentrations (MICs) were determined by the broth dilution method. Drug interactions were assessed by the checkerboard and time-kill methods. Synergy was defined by a fractional inhibitory concentration index (FICI) of ≤0.5 or a ≥2 log10 CFU/mL killing at 24 h with the combination in comparison with killing by the most active single agent. Indifference was defined by a FICI > 0.5-4.0 or a 1-2 log10 CFU/mL killing compared with the most active single agent. MICs of daptomycin were 2-4 μg/mL for E. faecalis and 2-8 μg/mL for E. faecium. MICs of linezolid were 1-2 μg/mL for all bacteria. In the checkerboard assay, five isolates showed synergism (FICI < 0.5) and two showed indifference (FICIs of 0.53 and 2). Killing studies revealed synergy of daptomycin plus linezolid against four isolates (2.2-3.7 log10 CFU/mL kill) and indifference (1.1-1.6 log10 CFU/mL kill) for the other three strains. Antagonism was not observed. In conclusion, the combination of daptomycin and linezolid had a synergistic or indifferent effect against multidrug-resistant enterococci. Additional studies are needed to explore the potential of this combination for severe enterococcal infections when first-line antibiotic combinations cannot be used.
Keywords
daptomycin, linezolid, synergy, Enterococcus faecalis, Enterococcus faecium
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Create date
20/01/2015 15:14
Last modification date
20/08/2019 15:40
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