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

BACKGROUND: Oritavancin (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. METHODS: A 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. RESULTS: Among 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 MIC(90) values (0.06 µg/mL) against SA and CoNS, inhibiting 98.8% of these isolates at ≤0.12 µg/mL. ORI MIC(50) values were 8- to 32-fold lower than those for vancomycin (VAN), daptomycin (DAP), and ceftaroline (CPT) against staphylococci. ORI showed MICs against EFM (MIC(50/90), 0.008/0.03 µg/mL) that were 2-fold lower than against EFC (MIC(50/90), 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 (MIC(50/90), ≤1/2 µg/mL), and linezolid (LZD) (MIC(50/90), 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 (MIC(90), 0.12 µg/mL) tested against VGS. CONCLUSION: ORI 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