P0469 In-vitro activity of oritavancin against daptomycin and/or linezolid resistant Enterococcus faecium clinical isolates: a single centre study

Abhay Dhand*1, Nicholas Feola1, Leslie Lee1, Guiqing Wang1

1Westchester Medical Center

Background: Oritavancin is a novel antibiotic with potent activity against a broad range of gram- positive organisms. Resistance to daptomycin, linezolid and other antibiotics among enterococcus is on the rise in many US hospitals. Oritavancin may provide an alternative antibiotic therapy for serious infections caused by such very resistant enterococci. The aim of this study was to evaluate in vitro antimicrobial susceptibility of oritavancin against enterococci with focus on Daptomycin non- susceptible (DNSE) and Linezolid resistant (LRE) clinical isolates.

Materials/methods: DNSE and LRE clinical isolates were recovered from patients in a tertiary medical center in suburban New York City from May 2015 through December 2016. Daptomycin susceptibility was determined by MicroScan WalkAway™ System and confirmed by E-test. Susceptibility of oritavancin and linezolid was performed by broth microdilution using the Sensititre™ panel in accordance with the guidelines of the Clinical and Laboratory Standards Institute and package insert of the manufacturer. The isolates were confirmed by analysis of 16S rRNA gene sequence or by the MALDI Biobiotyper CA System™.

Results: A total of 24 nonduplicate E. faecium clinical isolates were analyzed in this study. 19/24 isolates were DNSE (6-96 μg/ml), 4/24 were LRE (8-16 μg/ml) and 2/24 were both DNSE and LRE.

The MIC50 and MIC90 of oritavancin against combined resistant enterococci isolates was 0.06 μg/ml

and 0.25 μg/ml (range: 0.008 – 0.25 μg/ml) respectively. Oritavancin MIC50 values were 33 to 200 fold lower than those for linezolid and daptomycin against the study isolates. Overall, oritavancin susceptibility was seen in 17 of 19 (90%) DNSE isolates, 1 of 4 (25%) LRE isolates and in 0 of 2 (0%) DNSE+ LRE isolates. Oritavancin resistance along with daptomycin and linezolid resistance was significantly higher in sequence type (ST) 736 compared with non-ST 736 isolates (p<0.0001).

Conclusions: There is limited clinical data for treatment of resistant enterococcal infections using oritavancin. The greater potency, safety profile and in-vitro susceptibility data provides the microbiological basis for potential use of oritavancin in treatment of selected patients with infections caused by extremely resistant enterococci.