In-vitro activities of daptomycin in combination with rifampicin and gentamicin against VRE strains.

Doç. Dr. Gülseren Aktaş, İstanbul Tıp Fakültesi, Temel Tıp Bilimleri, Tıbbi Mikrobiyoloji Anabilim Dalı, Çapa, 34093 İstanbul, Türkiye Tel. 0555 379 45 57 Email. gulserena2001@yahoo.co.uk Geliş Tarihi: 05.03.2015 • Kabul Tarihi: 29.08.2016 ABSTRACT AIM: In-vitro activity of daptomycin in combination with rifampicin and gentamicin, was assessed against vancomycin-resistant enterococci (VRE) with both high-level aminoglycoside resistance (HLAR) and non-HLAR. METHODS: Identification of 39 VRE was performed using conventional methods. HLAR strains were identified by using disk diffusion method with gentamicin: 120 μg and streptomycin: 300 μg disks. The rates of HLAR and non-HLAR were established as 41% (16/39) and 59% (23/39), respectively. Minimum inhibitory concentration (MIC) of all antibiotics used were determined and evaluated using microbroth dilution technique as described by Clinical and Laboratory Standards Institute (CLSI). In-vitro activities of antibiotic combinations were determined using microbroth “checkerboard” microdilution technique. Fractional inhibitory concentration index (FICI) were calculated relative to MIC values of antibiotics both alone and in combinations. Synergy was defined as a FICI of ≤0.5, additive/indifference as a FICI >0.5–4.0 and antagonism as a FICI of >4.0. RESULTS: All strains were established as daptomycin susceptible (100%) while rifampicin susceptibility rate was found to be 5.1% (2/39) according to MICs. When daptomycin was combined with rifampicin and gentamicin, additive/indifferent effects were observed for the majority of 39 strains, even though the synergistic effect defined in non-HLAR were 34.8% and 8.7%, respectively. Although daptomycin combination with rifampicin showed a synergistic effect against 50% of HLAR, no synergism was observed in combination of daptomycin with gentamicin. The combinations of both daptomycin/rifampicin and daptomycin/gentamicin also showed FICI of 0.155–1.5 and 0.375–2 against strains, respectively. There was no antagonism observed in any of the combinations. CONCLUSION: The results of the study suggest that the combination of daptomycin/rifampicin may be recommended as an alternative in treatment of serious VRE infections caused by both HLAR and non-HLAR.