title: Comparative in vitro activity of oritavancin and other agents against methicillin-susceptible and methicillin-resistant Staphylococcus aureus.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a threat to the public health due to their prevalence and associated mortality and morbidity. Several agents have been recently approved to treat MRSA skin infections including lipoglycopeptides (dalbavancin, oritavancin, and telavancin), ceftaroline, and tedizolid. This study compared the MIC, minimum bactericidal concentration (MBC), and time-kill of these agents alongside daptomycin, linezolid, and vancomycin against MRSA (n=15); meropenem, cefazolin, and nafcillin were also included against methicillin-susceptible S. aureus (MSSA [n=12]). MIC and MBC testing was conducted in accordance with Clinical and Laboratory Standards Institute guidelines, and time-kills were evaluated at multiples of the MIC and the free-drug maximum plasma concentration (fCmax) at both standard and high inoculum densities for a subset of MRSA (n=2) and MSSA (n=2). MRSA and MSSA were highly susceptible to all agents, with the lipoglycopeptides having the most potent activity by MIC50/90. All agents excluding tedizolid and linezolid were bactericidal by MBC for MRSA and MSSA, though dalbavancin and telavancin exhibited strain-specific bactericidal activity for MRSA. All agents excluding tedizolid and linezolid were bactericidal by time-kill at their respective fCmaxagainst MRSA and MSSA at standard inoculum density, though oritavancin exhibited the most rapid bactericidal activity. Oritavancin and daptomycin at their respective fCmaxmaintained similar kill curves at high inoculum density. In contrast, the killing observed with other agents was typically reduced or slowed at high inoculum density. These data demonstrate the rapid bactericidal activity of oritavancin and daptomycin against S. aureus relative to other MRSA agents regardless of bacterial burden.
authors.affiliation: Micromyx, LLC, Kalamazoo, MI 49008, USA.
authors.forename: Debora
authors.initials: D
authors.lastname: Sweeney
authors.affiliation: Micromyx, LLC, Kalamazoo, MI 49008, USA.
authors.forename: Dean L
authors.initials: DL
authors.lastname: Shinabarger
authors.affiliation: The Medicines Company, Montreal, H2Y 3X7, Québec, Canada.
authors.forename: Francis F
authors.initials: FF
authors.lastname: Arhin
authors.affiliation: The Medicines Company, Montreal, H2Y 3X7, Québec, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Belley
authors.affiliation: The Medicines Company, Montreal, H2Y 3X7, Québec, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Moeck
authors.affiliation: Micromyx, LLC, Kalamazoo, MI 49008, USA. Electronic address: cpillar@micromyx.com.
authors.forename: Chris M
authors.initials: CM
authors.lastname: Pillar
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology*; D000077427:Lipoglycopeptides; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology; D014640:Vancomycin / Q000031:analogs & derivatives
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D000077427:Lipoglycopeptides; C100708:oritavancin; D014640:Vancomycin
keywords: Bactericidal activity; Lipoglycopeptides; MRSA