In Vitro Activity of Linezolid and Dalbavancin Against Vancomycin-Resistant Enterococci

Abstract

The incidence of infections caused by multidrug resistant gram-positive bacteria is increasing worlwide. In addition, emergence and dissemination of glycopeptide resistance in enterococci has accelerated the need for the development of new antimicrobial agents for treatment. Linezolid which is an oxazolidinone and dalbavancin which is a second-generation, semi-synthetic lipoglycopeptid are important therapeutic options for infections caused by antimicrobial-resistant gram-positive pathogens. The aim of this study was to investigate the in-vitro antimicrobial activity of linezolid and dalbavancin against vancomycin-resistant enterococci (VRE). A total of 100 VRE strains, isolated from rectal swabs of patients hospitalized in Istanbul University Faculty of Istanbul Medicine between 2006-2007 were included in the study. All strains were identified as Enterococcus spp. by conventional methods and had minimum inhibitory concentrations (MICs) of >= 32 mu g/ml for vancomycin. Vancomycin, linezolid and dalbavancin susceptibility testing was performed by broth microdilution method. For the quality control of the tests, S.aureus ATCC 2921 3 and E.faecalis ATCC 29212 were included in each run. Molecular identification of linezolid-resistant strains (n=2) were done by 16S rRNA sequencing and resistance mechanisms were tested by 23S rRNA sequencing. Against VRE strains, MIC50, MIC90 and MIC ranges of linezolid and dalbavancin were found as 4, 4, 1-16 mu g/ml and 32, 64, 0.25-128 mu g/ml, respectively. Linezolid susceptibility, intermediate susceptibility and resistance rates were found as 32%, 66% and 2% in the same order. Linezolid-resistant two strains were identified as E.faecium, and this data was confirmed by Pasteur Institute. Both of those isolates had G2576T mutations in 23S rRNA genes. Because susceptibility breakpoint for dalbavancin has not been established by Clinical and Laboratory Standards Institute (CLSI) yet, susceptibility and resistance rates for dalbavancin were not indicated. According to the MIC results, linezolid was found to be the most effective antibiotic against VRE strains, and dalbavancin was found more effective than vancomycin. Additionally, our results showed that routine susceptibility testing of VRE strains isolated from hospitalized patients to linezolid was required.