In vitro activity of daptomycin combinations with rifampicin, gentamicin, fosfomycin and fusidic acid against MRSA strains

Objectives: Although new antimicrobial agents designed to treat infections with limited therapeutic options have been introduced in the past few years, resistant Gram positive cocci have continued to emerge and spread. Daptomycin is a cyclic lipopeptide antibiotic that has rapid bactericidal activity against broad spectrum of Gram positive bacteria, including methicillin resistant Staphylococcus aureus (MRSA). Antibiotics are sometimes used in combination in an attempt to prevent or delay the in vivo emergence of drug-resistant subpopulations of pathogenic organisms. The aim of the study was to evaluate in vitro activity of daptomycin combinations with rifampicin, gentamicin, fosfomycin, and fusidic acid against MRSA strains. Methods: In total, 25 strains were tested. The minimum inhibitory concentrations of all antibiotics were determined using a microbroth dilution assay. The in vitro activities of antibiotics in combination were assessed using the microbroth checkerboard technique. With this method, the fractional inhibitory concentration index was interpreted as follows: synergism <= 0.5; additive/indifference > 0.5-<= 4; antagonism > 4. Results: According to the MIC values, all strains (100%) were susceptible to daptomycin, 16% (4/25) to rifampicin, 20% (5/25) to gentamicin, 44% (11/25) to fosfomycin, and 72% (18/25) to fusidic acid. Synergistic interaction of daptomycin in combinations with rifampicin, gentamicin, fosfomycin, and fusidic acid were found as 12%, 68%, 100% and 16%, respectively. No antagonism was observed. Conclusion: The combination of daptomycin with fosfomycin may be a promising alternative therapy of MRSA infections. (C) 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.