Comparative activity of oritavancin against meticillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates from Geneva University Hospital

In this study, we assessed by broth microdilution the in vitro activity of oritavancin, a semisynthetic lipoglycopeptide currently under development, against selected meticillin-resistant Staphylococcus aureus (MRSA) bloodstream isolates (n = 56) from Geneva University Hospital, Switzerland, displaying a wide range of vancomycin minimum inhibitory concentrations (MICs) (0.25-4 mu g/mL). The MRSA resistance phenotype was confirmed by broth microdilution (oxacillin MIC >= 4 mu g/mL) for all isolates; 89% and 100% of the tested isolates were also resistant to erythromycin and ciprofloxacin, respectively. For 53 MRSA isolates for which vancomycin MICs were in the susceptible range (0.5-2.0 mu g/mL), the oritavancin MICs ranged from 0.03 mu g/mL to 0.5 mu g/mL. For these 53 vancomycin-susceptible isolates, the cumulative distribution of oritavancin MICs was markedly different from those of vancomycin, teicoplanin, daptomycin and linezolid MICs, yielding an oritavancin MIC for 90% of the organisms (MIC(90)) (0.25 mu g/mL) that was four times lower than the MIC(90) values (1 mu g/mL) of comparators. For three MRSA isolates with a vancomycin-intermediate phenotype (vancomycin MIC = 4 mu g/mL), oritavancin MICs (0.5-1.0 mu g/mL) were 2-4-fold lower than vancomycin, teicoplanin or daptomycin MICs, but were equivalent to linezolid MICs. Pairwise comparison for each bloodstream isolate showed that oritavancin was >= 4-fold more active than vancomycin, teicoplanin and daptomycin, against 86%, 75% and 59% of all MRSA isolates, respectively. (C) 2009 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.