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Daptomycin-Nonsusceptible Staphylococcus aureus: The Role of Combination Therapy with Daptomycin and Gentamicin

Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia
Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria 3004, Australia
Author to whom correspondence should be addressed.
Academic Editors: Jonathan Iredell and Sally Partridge
Genes 2015, 6(4), 1256-1267;
Received: 19 August 2015 / Revised: 5 November 2015 / Accepted: 16 November 2015 / Published: 30 November 2015
(This article belongs to the Special Issue Antibiotic Resistance: Mobility and Microbiomes)
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Reduced susceptibility to daptomycin in Staphylococcus aureus has now been described, leading to clinical failures. Here we determined the impact of daptomycin and gentamicin combination therapy on bactericidal activity and resistance emergence using daptomycin-susceptible and -resistant isolates with mutations linked to previous daptomycin or vancomycin exposure. Enhanced killing of S. aureus was observed when gentamicin was combined with daptomycin, most commonly with daptomycin concentrations below the peak serum free-drug concentrations achieved with standard dosing. Synergy was seen with daptomycin-susceptible isolates and with isolates resistant to vancomycin and daptomycin. Combination therapy also prevented the emergence of resistance. Daptomycin and gentamicin combination therapy may provide the synergy required to prevent emergence of resistance when daptomycin levels are below peak serum concentrations as would be found in deep-seated, complicated infections. View Full-Text
Keywords: S. aureus; synergy; time-kill studies; VISA; MRSA; combination therapy S. aureus; synergy; time-kill studies; VISA; MRSA; combination therapy

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Jiang, J.-H.; Peleg, A.Y. Daptomycin-Nonsusceptible Staphylococcus aureus: The Role of Combination Therapy with Daptomycin and Gentamicin. Genes 2015, 6, 1256-1267.

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