Analysis of Oritavancin Activity against Gram-Positive Clinical Isolates Responsible for Bacterial Endocarditis in United States and European Hospitals (2008–2016)

Abstract

BackgroundOritavancin (ORI) has documented in vitro activity against gram-positive (GP) isolates. This study analyzed ORI tested against organisms causing endocarditis in United States (US) and European (EU) sites.MethodsA total of 424 organisms recovered from patients with a diagnosis of bacterial endocarditis at US and EU sites during the SENTRY Antimicrobial Surveillance Program (2008–2016) were included (see Table). Isolates were identified by standard biochemical algorithms and MALDI-TOF. Susceptibility (S) testing was performed by CLSI methods, and MICs were interpreted per CLSI and/or EUCAST criteria.ResultsAmong the 424 isolates, 212 (50.0%) were S. aureus (SA; 31.6% methicillin-resistant [MRSA]), 47 (11.1%) were coagulase-negative staphylococci (CoNS), 81 (19.1%) were E. faecalis (EFC), 21 (5.0%) were E. faecium (EFM), 24 (5.7%) were BHS, and 39 (9.2%) were viridans group streptococci (VGS). ORI had similar MIC90 values (0.06 µg/mL) against SA and CoNS, inhibiting 98.8% of these isolates at ≤0.12 µg/mL. ORI MIC50 values were 8- to 32-fold lower than those for vancomycin (VAN), daptomycin (DAP), and ceftaroline (CPT) against staphylococci. ORI showed MICs against EFM (MIC50/90, 0.008/0.03 µg/mL) that were 2-fold lower than against EFC (MIC50/90, 0.015/0.03 µg/mL; 97.5%S against all or 100%S against indicated VAN-S isolates). ORI inhibited 98.0% of all enterococci, including VAN-resistant isolates at ≤0.12 µg/mL. VAN, DAP, ampicillin (MIC50/90, ≤1/2 µg/mL), and linezolid (LZD) (MIC50/90, 1/2 µg/mL) were similarly active against EFC, while DAP and LZD had coverage (100.0%S) against EFM. Overall, BHS were highly S to all agents tested, except for erythromycin (70.8%S) and tetracycline (43.5%S). ORI was the most active agent (MIC90, 0.12 µg/mL) tested against VGS.ConclusionORI showed potent in vitro activity against isolates recovered from patients with endocarditis in US and EU sites. The data presented here warrant further investigations to determine whether ORI has a role for treating endocarditis.Disclosures M. A. Pfaller, The Medicines Company: Research Contractor, Research grant; H. S. Sader, The Medicines Company: Research Contractor, Research grant; D. Shortridge, The Medicines Company: Research Contractor, Research grant; R. K. Flamm, The Medicines Company: Research Contractor, Research grant; R. E. Mendes, The Medicines Company: Research Contractor, Research grant