万古霉素单用及联合利福平或磷霉素对耐甲氧西林金黄色葡萄球菌防耐药突变浓度的研究  

Study on mutant prevention concentrations of vancomycin alone and in combination with rifampicin or fosfomycin against MRSA

作　　者：梅清[1] 喻婷[1] 朱玉林[1] 程君[1,2,3] 叶英[1,2,3] 李家斌[1,2,3] 

机构地区：[1]安徽医科大学第一附属医院感染科安徽省细菌耐药监测中心,安徽合肥230022 [2]安徽省细菌耐药监测中心,安徽合肥230022 [3]安徽医科大学细菌耐药研究所,安徽合肥230022

出　　处：《中国药理学通报》2011年第7期944-947,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No81071394)

摘　　要：目的在体外探讨万古霉素单用及其分别与利福平、磷霉素联合使用对耐甲氧西林金黄色葡萄球菌(methicillin-resistant staphylococcus aureus,MRSA)防耐药突变浓度的影响,为防止细菌耐药的产生提供理论依据。方法应用肉汤法富集浓度为1010 CFU.ml-1细菌,琼脂平板倍比稀释法测定上述抗菌药物单用及联合使用对10株MRSA临床分离株的防耐药突变浓度,并计算相应的选择指数和耐药频率。结果万古霉素单用对上述10株MRSA的选择指数为16～64;分别与利福平、磷霉素联合使用选择指数下降为2～16和1～8,联合用药较单独用药选择指数下降2～32倍,其耐药频率也大幅下降。结论万古霉素分别与利福平、磷霉素联合使用均可降低其单用对MRSA的防耐药突变浓度,缩小耐药突变选择窗,防止耐药突变菌的产生。Aim To evaluate the mutant prevention concentrations of vancomycin alone and in combination with rifampiein and fosfomyein against Methicillin-re- sistant staphylococcus aureus （MRSA） in vitro, which provides evidence for new strategies for restricting the development of resistance. Methods The cells of 10^10 colony forming units per milliliter coccus were enriched in broth. Mutant prevention concentrations of the above drugs for 10 strains of MRSA were detected with agar dilution method and the value of selectiveity index and drug-resistant frequencies were calculated. Results The selectiveity index of vancomycin alone for 10 strains of MRSA were 16 -64, and selectiveity index of the combination application with rifampicin and fos-fomycin for MRSA were 2 - 16 and 1 - 8 respectively. The selectiveity index for the combination application decreased 2 to 32-fold and drug-resistant frequencies were also significantly lower than the single application of vancomycin. Conclusion Combinations use of antimicrobial agents can decrease the mutant prevention concentration of MRSA and narrow the mutant selection window, so the emergences of resistant strains are decreased.

关 键 词：耐甲氧西林金黄色葡萄球菌 万古霉素 利福平 磷霉素 联合用药 防耐药突变浓度 耐药突变选择窗 耐药频率 

分 类 号：R378.11[医药卫生—病原生物学] R978.1[医药卫生—基础医学]