利奈唑胺对耐甲氧西林金黄色葡萄球菌细菌生物膜的抑制与消除活性及体内外抗菌活性研究

Activity of Linezolid against Methicillin-Resistant Staphylococcus Aureus Biofilm and Its Antimicrobial Activity in Vitro and in Vivo

目的系统性评价利奈唑胺对2013-2014年耐甲氧西林金黄色葡萄球菌（MRSA ）临床分离株细菌生物膜（BBF） 的活性及体内外抗菌效果.方法：体外试验测定最低抑菌浓度（MIC ）;最低杀菌浓度（MBC ）;最小抑制B B F 浓度（M B IC ）和最低B B F 消除浓度（MBEC ）;活菌计数法绘制时间-杀菌曲线（KCs）;体内试验采用小鼠M R S A 全身感染模型,尾静脉给药保护小鼠后测定半数有效剂量（EDso）;建立免疫低下小鼠M R S A 大腿感染模型,记录尾静脉给药24 h后大腿组织菌量的变化.结果：利奈唑胺对2013-2014年临床分离的6 0 株M R S A 均敏感;对金黄色葡萄球菌B B F 的M B IC 值与万古霉素相当,敏感性显著高于阿莫西林;体内试验中,利奈唑胺对全身感染小鼠有很好的治疗效果,EDso小于万古霉素与阿莫西林;对免疫低下M R S A 大腿感染模型小鼠的保护作用也要优于万古霉素和阿莫西林.结论：利奈唑胺对2013-2014年分离的M RS A临床菌株体内外活性均较高,尤其对M RS A的细菌生物膜也显示了极强的抑制作用.

Objective: To systematically research the antimicrobial activity of Linezolid against methicillin-resistant Staphylococcus aureus (MRSA) from 2013~2014 in vitro and in vivo. Methods:Minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), minimal bacterial biofilm inhibitory concentration (MBIC) and minimal bacterial biofilm eradication concentration (MBEC) were determined in vitro. The time-killing curves (KCs) were drawn by live bacteria counting method. In vivo tests, the model of systemic infection with MRSA was established in mice, the mice were treated with linezolid by intravenous injection for the calculation of ED50. With the established immunodeficiency mouse model of thigh infection with MRSA, CFU in the thighs were counted 24 hours after the administration of linezolid by intravenous injection. Results: Linezolid was sensitive to all 60 clinically isolated MRSA. The MBIC of linezolid against MRSA bacterial biofilm were similar to those of Vancomycin, its sensitivity was significantly higher than that of Amoxicillin. In vivo, linezolid had better effects against systemic MRSA infection and thigh muscle MRSA infection compared with those of Vancomycin and Amoxicillin. Conclusion: Linezolid has excellent antibacterial activity against MRSA in vitro and in vivo.