中药影响金黄色葡萄球菌对氟喹诺酮类药物耐药突变选择窗MSW及耐药性变化的研究论文.pdfVIP

目 录 中药影响金黄色葡萄球菌对氟喹诺酮类药物的耐药突变选择 1 窗MSW 及耐药性变化的研究„„„„„„„„„„„„„ 1.1 中文摘要„„„„„„„„„„„„„„„„„„„„„1 1.2 英文摘要„„„„„„„„„„„„„„„„„„„„„3 1.3 前言„„„„„„„„„„„„„„„„„„„„„„„5 第一部分 中药联合左氧氟沙星影响左氧氟沙星对金黄色葡 1.4 萄球菌的耐药突变选择窗MSW 的体外研究 1 材料与方法„„„„„„„„„„„„„„„„„„„8 2 结果„„„„„„„„„„„„„„„„„„„„„„18 3 讨论„„„„„„„„„„„„„„„„„„„„„„18 第二部分 中药联合左氧氟沙星影响左氧氟沙星对金黄色葡 1.5 萄球菌的耐药突变选择窗MSW 的体内研究 1 材料与方法„„„„„„„„„„„„„„„„„„„7 2 结果„„„„„„„„„„„„„„„„„„„„„„18 3 讨论„„„„„„„„„„„„„„„„„„„„„„19 1.6 结论„„„„„„„„„„„„„„„„„„„„„„„21 1.7 参考文献„„„„„„„„„„„„„„„„„„„„„25 2 致谢„„„„„„„„„„„„„„„„„„„„„„„26 耐药突变选择窗理论的研究与意义 （综述）„„„„„29 3 中药影响金黄色葡萄球菌对氟喹诺酮类药物的耐药突变选 择窗MSW 及耐药性变化的研究 摘 要 目的：探讨中药制剂与左氧氟沙星联合应用对金黄色葡萄球菌的抑菌 作用，并考察其对左氧氟沙星的耐药突变选择窗(MSW)的影响，为临 床减少氟喹诺酮类抗菌药物的耐药产生提供一种全新的治疗策略。方 法：体外研究尝试用琼脂平板二倍稀释法测定双黄连粉针，喜炎平注 射剂，大蒜素注射剂3 种中药制剂对标准金黄色葡萄球菌的最低抑菌 浓度（MIC）、防耐药变异浓度（MPC）并计算其治疗指数(SI）。再将 以上中药制剂与左氧氟沙星联用以考察以上中药制剂是否能缩窄左 氧氟沙星的MSW，并筛选出抗菌效果较好且对降低左氧氟沙星的MSW 影响最大的中药制剂做进一步的体内研究，以考察中药制剂是否能在 体内降低左氧氟沙星的 MSW 。结果：双黄连的 MSW 为 1.905～ 14.737mg/ml,SI 为7.736；大蒜素的MSW 为5.960～38.500 μg/ml， SI 为6.460。喜炎平的MSW 未测得。双黄连与左氧氟沙星联用在体外 可将左氧氟沙星的SI 显著降低，而大蒜素对左氧氟沙星的SI 和MSW 几乎没有作用。体内实验表明左氧氟沙星+双黄连组的耐药发生率低 于单用左氧氟沙星组。结论：3 种中药注射剂对金黄色葡萄球菌有一 定的抑制作用，体外实验显示双黄连可明显降低左氧氟沙星的 SI。 体内实验表明左氧氟沙星+双黄连组的耐药发生率低于单用左氧氟沙 星组。 关键词：中药制剂;左氧氟沙星；MSW Chinese medicine preparations associated with levofloxacin resistance changes in vivo and in Staphylococcus aureus Abstract: bjective: Explore the inhibitory role of traditional Chinese medicine preparation of Staphylococcus aureus in combination with levofloxacin, investigated levofloxacin resistance mutations to select the window (MSW), to reduce the resistance of fluoroquinolones for clinical provide a newtherapeutic strategies. Methods : Try in vitro st