title: In vitro activities of oritavancin and comparators against meticillin-resistant Staphylococcus aureus (MRSA) isolates harbouring the novel mecC gene.
abstract: Meticillin-resistant Staphylococcus aureus (MRSA) is routinely detected by amplification of the mecA gene. Recently, MRSA isolates harbouring a novel mec gene (mecC) that is not detected by mecA amplification have been reported. In this study, the activities of the lipoglycopeptide oritavancin as well as the comparators vancomycin, daptomycin and linezolid against 14 mecC MRSA isolates were studied by broth microdilution minimum inhibitory concentration (MIC) and time-kill assays at clinically relevant concentrations of each antibacterial agent. Oritavancin, vancomycin, daptomycin and linezolid MIC90 values (MIC required to inhibit 90% of the isolates) against the mecC isolates were 0.06, 1, 1 and 2mg/L, respectively. In time-kill assays, oritavancin at concentrations reflective of its free peak in plasma of patients receiving a single 1200 mg intravenous dose and the level 24h thereafter was bactericidal against all isolates tested, attaining 3 log kill relative to the starting inoculum between 5 min and 15 min. Vancomycin both at its free peak and free trough concentrations was also bactericidal against all isolates, attaining bactericidal activity between 6h and 24h. Daptomycin was bactericidal only at its free peak concentration, attaining bactericidal activity between 30 min and 4h against the tested isolates. Linezolid was bacteriostatic (<3 log kill relative to the starting inoculum) against the tested isolates. Oritavancin's in vitro activity against mecC MRSA isolates was indistinguishable from that against mecA MRSA isolates both in MIC and time-kill assays.
authors.affiliation: The Medicines Company, 7170 Frederick Banting, St Laurent, Quebec, Canada H4S 2A1. Electronic address: francis.arhin@themedco.com.
authors.forename: Francis F
authors.initials: FF
authors.lastname: Arhin
authors.affiliation: The Medicines Company, 7170 Frederick Banting, St Laurent, Quebec, Canada H4S 2A1.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Sarmiento
authors.affiliation: The Medicines Company, 7170 Frederick Banting, St Laurent, Quebec, Canada H4S 2A1.
authors.forename: Gregory
authors.initials: G
authors.lastname: Moeck
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D017576:Daptomycin / Q000494:pharmacology; D015870:Gene Expression; D006020:Glycopeptides / Q000494:pharmacology*; D000069349:Linezolid; D000077427:Lipoglycopeptides; D016106:Methicillin Resistance / Q000235:genetics*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D023303:Oxazolidinones / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology / Q000031:analogs & derivatives
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006020:Glycopeptides; D000077427:Lipoglycopeptides; D023303:Oxazolidinones; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin; C100708:oritavancin
keywords: MRSA; Oritavancin; mecC