1583. Eight Years of Sustained Potency and Activity of Oritavancin against Gram-Positive Isolates Causing Bacteremia and Endocarditis in the USA, Including Enterococcal Infections Requiring an Optimized Dosing Strategy for Daptomycin

Abstract

BackgroundOritavancin (ORI) is a potent lipoglycopeptide with desirable PK/PD parameters for treating serious gram-positive infections. This study assessed the activity of ORI against Staphylococcus aureus (SA), Enterococcus faecalis (EF), and E. faecium (EFM) causing bloodstream infection (BSI), including infective endocarditis (IE) and daptomycin (DAP)- susceptible dose-dependent (SDD) vancomycin-resistant (VRE) subsets. We also evaluated the longitudinal activity of ORI.MethodsA total of 5,469 SA, 1,157 EF, and 721 EFM were recovered from BSI in 35 US sites (2011–2018). Subsets of SA isolates causing IE (84) and EFM displaying DAP-SDD-VRE phenotypes (230) were included. Identification was confirmed by MALDI-TOF MS and isolates were tested for susceptibility (S) according to CLSI.ResultsOverall, ORI showed similar MIC50 (0.03 mg/L) and MIC90 results (0.06 mg/L) against MRSA and MSSA (figure) and the SA EC subset (41.7% MRSA; data not shown). Similar findings were noted for ORI tested against EF DAP-S (MIC50/90, 0.015/0.06 mg/L) and DAP-SDD (MIC50/90, 0.015/0.06 mg/L). ORI MIC values against DAP- and VAN-S EFM (MIC50/90, ≤0.008/0.015 mg/L) were at least 8-fold lower than those from DAP-SDD-VRE isolates (MIC50/90, 0.06/0.12 mg/L; 31.9% of all EFM), and all EFM were inhibited by ORI at ≤0.25 mg/L. The longitudinal analysis showed MRSA rates varying from 39.7% (2017) to 46.8% (2011), while the annual ORI MIC50 and MIC90 results were 0.015–0.06 mg/L and 0.03–0.12 mg/L, respectively, against MRSA during the 8-year period. ORI yearly MIC50 and MIC90 results were 0.015–0.03 mg/L and 0.03–0.12 mg/L against EF, respectively. MIC50 and MIC90 results of 0.008–0.03 mg/L and 0.03–0.12 mg/L, respectively, were obtained for ORI against the DAP-SDD EF subset each year. ORI MIC50 and MIC90 results of 0.03–0.06 and 0.06–0.12 mg/L were obtained annually against DAP-SDD-VRE (EFM), respectively.ConclusionORI showed a potent activity against this collection of isolates causing BSI and IE in the USA, including resistant subsets requiring higher dosage regimens when treating serious infections. In addition, ORI maintained a stable potency throughout the 8-year study period with no apparent temporal trends. Disclosures All authors: No reported disclosures.