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Abstract

The aim of this study was to evaluate the activity of double-carbapenem combinations against OXA-48-producing clinical isolates.

Double combinations of ertapenem, meropenem and imipenem were evaluated for synergy and bactericidal activity using the time–kill methodology. All antibiotics were tested at 10 mg l and at a sub-inhibitory concentration of 0.5× minimum inhibitory concentration (MIC) for isolates with a carbapenem MIC≤8 mg l. Synergy was defined as a ≥2log colony-forming units (c.f.u.) ml decrease of viable colonies at 24 h compared to the most active carbapenem alone.

Ten distinct clinical isolates were tested. All carried and , and exhibited an MIC range of 64–128, 4–32 and 1–32 mg l for ertapenem, meropenem and imipenem, respectively. Out of 48 isolate-combinations, synergy was observed in 9 (18.8 %) and cidal activity was observed in 13 (27.1 %). synergistic activity was noted for 5 out of 29 (17.2 %) ertapenem-, 6 out of 29 (20.7 %) meropenem- and 7 out of 38 (18.4 %) imipenem-containing combinations. No combination exhibited antagonism. Bactericidal activity was observed in 7 (24.1 %) ertapenem-, 8 (27.6 %) meropenem- and 11 (28.9 %) imipenem-containing combinations. Among the sub-inhibitory concentration combinations, three (15 %) ertapenem-, four (20 %) meropenem- and three (15 %) imipenem-containing ones showed synergistic interaction.

Dual combinations of carbapenems, including those containing sub-inhibitory concentrations of antibiotics, were synergistic against multidrug-resistant (MDR) and extensively drug-resistant (XDR) isolates harbouring .

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2018-05-01
2024-04-20
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