Background: Oritavancin (ORI) was approved in the USA (2014) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by Gram-positive pathogens. ORI in vitro activity was assessed against S. aureus causing invasive community- (CA) and hospital-associated (HA) infections.
Methods: 1,110 S. aureus were recovered from blood during the oritavancin resistance surveillance program for USA (2013 – 2014). Of these, 790 and 218 were defined as CA and HA, respectively, according to CDC definitions; 102 isolates were of unknown origin. Isolates were collected from 29 sites in the nine USA Census regions and were identified by standard algorithms and MALDI-TOF. Susceptibility testing was performed by CLSI methods (M07-A10); interpretation of MIC results used FDA (ORI), CLSI (2015) and/or EUCAST (2015) criteria. MRSA resistant to three or more drug classes were defined as multidrug-resistant (MDR).
Results: ORI (100.0% susceptible) had MIC50, MIC90 and MIC100 values of 0.03/0.06/0.12 mg/ml against S. aureus, regardless of susceptible phenotype or origin (Table). Other agents, including vancomycin (VAN), daptomycin (DAP) and linezolid (LZD) were active against all subsets. ORI MICs were 8-fold lower than DAP and 16- to 32-fold lower than VAN or LZD. All agents showed antimicrobial coverage (≥92.0% susceptible) against MSSA, except for erythromycin (ERY) against the CA-MSSA subset, and ERY (60.4% susceptible) and levofloxacin (LEV; 84.2% susceptible) against HA-MSSA isolates. ERY, LEV and clindamycin (CLI) resistance rates in HA-MRSA were slightly higher than those found in CA-MRSA (82.1 vs 80.9%, 77.8 vs 69.4% and 38.5 vs 29.9%, respectively). ORI, VAN, DAP, LZD, tetracycline and trimethoprim/sulfamethozaxole were active in vitro against CA- and HA-MRSA (94.0 – 100.0% susceptible). ORI, VAN, DAP and LZD showed consistent coverage against MDR MRSA, regardless of origin.
Conclusion: ORI had potent in vitro activity against this contemporary collection of CA and HA S. aureus causing invasive infections in USA hospitals. ORI in vitro potency was consistently greater than comparator agents.
R. E. Mendes,
The Medicines Company:
R. K. Flamm, The Medicines Company: Research Contractor , Research support
D. J. Farrell, The Medicines Company: Research Contractor , Research support
R. N. Jones, The Medicines Company: Research Contractor , Research support
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