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Oritavancin Activity Against Gram-positive Clinical Isolates Responsible for Documented Skin and Skin Structure Infections in USA and European Hospitals (2012-2013)

Abstract

Background.  Oritavancin (ORI) is under regulatory review in the USA and Europe for the treatment of acute bacterial skin and skin structure infections (SSSI) caused by Gram-positive pathogens. The ORI activity was assessed against contemporary isolates causing SSSI. Methods.  8,428 isolates from documented SSSI were collected from 27 sites in the USA and 34 sites in Europe, Israel and Turkey as part of the SENTRY Antimicrobial Surveillance Program (2012-2013). Bacteria were identified by standard algorithms and MALDI-TOF. Susceptibility testing was performed by CLSI methods (M07-A9); interpretation of MIC results used CLSI (2014) and EUCAST (2014) criteria Results.  ORI had MIC50/90 values of 0.03/0.06 µg/ml against S. aureus, which were ≥8-fold lower than those obtained for vancomycin (VAN; MIC50/90, 1/1 µg/ml), daptomycin (DAP; MIC50/90, 0.25/0.5 µg/ml) or linezolid (LZD; MIC50/90, 1/1 µg/ml). These agents had equivalent MIC50/90 values against methicillin-susceptible (MSSA) and -resistant S. aureus (MRSA). ORI MIC50/90 values against coagulase-negative staphylococci (CoNS; MIC50/90, 0.03/0.06 µg/ml) were ≥8-fold lower than comparators. VanA-phenotype E. faecalis had ORI MIC values (MIC50/90, 0.25/0.5 µg/ml) 16-fold higher than those obtained for VAN-susceptible isolates (MIC50/90, 0.015/0.03 µg/ml); nevertheless, ORI was ≥2-fold more active than DAP (MIC50/90, 0.5/1 µg/ml) or LZD (MIC50/90, 1/1 µg/ml) against VanA E. faecalis. ORI (MIC50/90, 0.004/0.008 µg/ml) had equivalent MIC values against VanB and VAN-susceptible E. faecium and higher MIC values (MIC50/90, 0.03/0.12 µg/ml) against VanA strains. However, ORI MIC values against VanA E. faecium were 8- to -64 lower than active (100% susceptible) comparators (DAP, MIC50/90, 2/4 µg/ml; and LZD, MIC50/90, 1/1 µg/ml). ORI had potent activity against S. pyogenes (MIC50/90, 0.03/0.12 µg/ml), S. agalactiae (MIC50/90, 0.03/0.06 µg/ml) and the S. anginosus group (MIC50/90, 0.008/0.015 µg/ml), with slightly higher MIC results against S. dysgalactiae (MIC50/90, 0.06/0.25 µg/ml). Conclusion.  ORI had potent activity in vitro against this contemporary collection of Gram-positive isolates causing SSSI. These results benchmark ORI activity prior to becoming clinically available. Disclosures.   R. E. Mendes, The Medicines Company: Grant Investigator, Research grant H. S. Sader, The Medicines Company: Grant Investigator, Research grant R. K. Flamm, The Medicines Company: Grant Investigator, Research grant D. J. Farrell, The Medicines Company: Grant Investigator, Research grant R. N. Jones, The Medicines Company: Grant Investigator, Research grant