The Medicines Company, 7170 Frederick Banting, St Laurent, Quebec, Canada H4S 2A1.
The Medicines Company, 7170 Frederick Banting, St Laurent, Quebec, Canada H4S 2A1.
Int J Antimicrob Agents. 2014 Jul;44(1):65-8. doi: 10.1016/j.ijantimicag.2014.03.015. Epub 2014 May 23.
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.
耐甲氧西林金黄色葡萄球菌(MRSA)通常通过扩增 mecA 基因来检测。最近,已经报道了携带新型 mec 基因(mecC)的 MRSA 分离株,该基因不能通过 mecA 扩增检测到。在这项研究中,通过肉汤微量稀释最小抑菌浓度(MIC)和时间杀伤试验,研究了利奈唑胺、万古霉素、达托霉素和奥利万星对 14 株 mecC-MRSA 分离株的活性,在每个抗菌药物的临床相关浓度下。奥利万星、万古霉素、达托霉素和利奈唑胺对 mecC 分离株的 MIC90 值(抑制 90%分离株所需的 MIC)分别为 0.06、1、1 和 2mg/L。在时间杀伤试验中,奥利万星在反映其在接受单次 1200mg 静脉剂量的患者血浆中游离峰浓度和此后 24 小时的浓度下,对所有测试分离株均具有杀菌作用,在 5 分钟至 15 分钟之间相对于起始接种物达到 3 对数杀灭。万古霉素在其游离峰和游离谷浓度下对所有分离株均具有杀菌作用,在 6 小时至 24 小时之间达到杀菌活性。达托霉素仅在其游离峰浓度下具有杀菌活性,在 30 分钟至 4 小时之间对测试分离株达到杀菌活性。利奈唑胺对测试分离株呈抑菌作用(相对于起始接种物的杀灭率<3 对数)。奥利万星对 mecC-MRSA 分离株的体外活性与 mecA-MRSA 分离株在 MIC 和时间杀伤试验中均无差异。