利奈唑胺、万古霉素对甲氧西林耐药的金黄色葡萄球菌的防耐药突变体选择浓度的研究

Mutant prevention concentrations study of linezolid and vancomycin against methicillin-resistant staphylococcus aureus isolates

目的:比较利奈唑胺、万古霉素对耐甲氧西林金黄色葡萄球菌的防耐药突变选择能力;研究防耐药突变体选择浓度(MPC)和最低抑菌浓度(MIC)的相关性。方法:采用琼脂微量稀释法测定利奈唑胺、万古霉素对35株耐甲氧西林金黄色葡萄球菌(MRSA)临床分离菌株的MPC和MIC;采用线性回归法比较利奈唑胺、万古霉素对MRSA的MPC和MIC的相关性;结合人体药代动力学数据,预测利奈唑胺、万古霉素对MRSA的防耐药突变体选择能力。结果:利奈唑胺、万古霉素对35株MRSA的MPC90值(抑制90%的细菌发生细菌耐药的最低防耐药突变体选择浓度)分别为16、8μg/mL,选择指数(MPC90/MIC90)均为8。两药对MRSA的MPC和MIC的线性相关系数R2分别为0.32和0.008。结合两药药代动力学参数,利奈唑胺药物浓度在整个给药间隔落在耐药突变选择窗理论(MSW)中,万古霉素药物浓度在大部分给药间隔落在MPC之上。结论:万古霉素对MRSA的防耐药选择能力强于利奈唑胺;MPC和MIC的相关性差。

AIM：To compare the mutant prevention concentration （MPC） of linezolid and vancomycin against methicillin resistant staphylococcus aureus（MRSA） and study the correlation between minimal inhibitory concentration （MIC） and MPC. METHODS： MICs and MPCs of two drugs against 35 MRSA clinical stains were determined by agar plates dilution method. The correlations between MIC and MPC were determined by linear regression. The ability to restrict the resistance was evaluated according the pharmacokinetics of two drugs. RESULTS： The MPCs of two drugs against MRSA were 16 and 8 μg/mL and the MPC/MIC was 8. MPCs and MICs correlated poorly （R^2 were 0. 32 and 0. 008, respectively）. According to pharmacokinetics of two drugs, the concentration of linezolid was inside the MSW（mutant selective window） for the entire dosage interval, while the concentration of vancomycin exceeded the MPC for the most dosage interval. CONCLUSION. The capacity of vancomycin for restricting the selection of MRSA resistant mutants is stronger than that of linezolid. There is low correlation between MPC and MIC.