Evaluation of Oritavancin Antimicrobial Activity Tested against Staphylococcus aureus Associated with Skin and Skin-Structure Infections (2008 - 2009)

Background: Oritavancin is under clinical development for therapy of acute bacterial skin and skin-structure infections (ABSSSI). This study provides a comprehensive evaluation of the activities of oritavancin and comparators tested against contemporary (2008 − 2009) S. aureus from documented ABSSSI. The analysis includes categorization of methicillin-resistant S. aureus (MRSA) according to drug resistance patterns. Methods: 1,789 and 2,085 S. aureus isolates were collected from 14 European countries (27 sites), including Israel and Turkey, and USA (27 sites), respectively. Identification was performed by standard algorithms and Vitek 2. S. aureus were tested for susceptibility by CLSI methods (M07-A8 and M100-S20-U). MRSA were categorized based on resistance patterns. Multidrug resistance (MDR) was defined when a resistance phenotype was noted for at least four antimicrobial classes. Results: Overall, oritavancin (MIC 50/90 , 0.03/0.06 µg/mL) was 8- to 64-fold more active than daptomycin (MIC 50/90 , 0.25/0.5 µg/mL; 100.0% susceptible), vancomycin (MIC 50/90 , 1/1 µg/mL; 100% susceptible) and linezolid (MIC 50/90 , 2/2 µg/mL; >99.9% susceptible). Trimethoprim/sulfamethoxazole (MIC 50/90 , ≤0.5/≤0.5 µg/mL; 99.0% susceptible) and tetracycline (MIC 50/90 , ≤2/2 µg/mL; 93.2% susceptible) also showed acceptable coverage (≥90% susceptible) against all S. aureus. A total of 1,661 (42.9%) strains were MRSA (Table), which displayed four main resistance patterns, including MDR (24.7%). Oritavancin showed modal and MIC 50 values of 0.03 µg/mL across nearly all resistant subsets. The activity of daptomycin (MIC 50 , 0.25 µg/mL), vancomycin (MIC 50 , 1 µg/mL) and linezolid (MIC 50 , 2 µg/mL) against MRSA was not affected by methicillin susceptibility phenotype. Clindamycin (96.5% susceptible) and levofloxacin (94.0% susceptible) were only active against methicillin-susceptible S. aureus. Oritavancin was 2-fold less active against MRSA with vancomycin MIC of 2 µg/mL (n=41; MIC 50/90 , 0.06/0.12 µg/mL) compared to strains with vancomycin MIC at ≤1 µg/mL (MIC 50/90 , 0.03/0.06 µg/mL). Conclusion: Oritavancin demonstrated potent activity against this collection of S. aureus causing ABSSSI. Oritavancin was slightly (2-fold) less active against MRSA with elevated vancomycin MICs (2 µg/mL), although inhibiting all tested strains at ≤0.25 µg/mL.