目的 总结华西医院艰难梭菌腹泻致病株的药物敏感性，比较其变迁，为艰难梭菌感染的治疗和防控提供基础参考数据。方法 分离四川大学华西医院2015年8～12月(44株)和强化感染控制措施后2016年7月至2017年7月(29株)两个时间段中腹泻患者粪便样本艰难梭菌致病产毒株共73株，PCR扩增毒素基因后进行测序鉴定。琼脂对倍稀释法测定甲硝唑、万古霉素、克林霉素、莫西沙星、四环素、利福昔明、非达霉素和硝唑尼特9种药物的最低抑菌浓度（MIC）。分析艰难梭菌耐药性，并对比强化感染控制措施前后的耐药性变化。结果 所有菌株对甲硝唑和万古霉素高度敏感，对克林霉素、莫西沙星、四环素、利福昔明的耐药率分别为79.5%、26.0%、27.4%、9.5%；对非达霉素和硝唑尼特高度敏感，两药的MIC范围均为<0.008～0.5 mg/L。与2015年相比，强化感染控制措施后艰难梭菌对克林霉素耐药率（99.5% vs. 44.8%）、莫西沙星耐药率（36.4% vs. 10.3%）下降，差异均有统计学意义（ P<0.05）。此外，发现一株罕见的利奈唑胺药物敏感性下降的菌株，其MIC 达16 mg/L。结论 华西医院艰难梭菌对克林霉素和莫西沙星的耐药率较高，需限制使用；对甲硝唑和万古霉素高度敏感，可以经验性使用。
英文摘要:
Objective To summarize the drug sensitivity and its trends of Clostridium difficile diarrhea pathogenic strains in a large tertiary hospital, so as to provide basic reference data for the treatment and control of Clostridium difficile infection. Methods There were 73 toxigenic isolates collected from fecal sample of diarrheal patients in West China Hospital of Sichuan University during two periods. One was from August to December in 2015 （44 strains）, and another was from July 2016 to July 2017 （29 strains）. Enhanced nosocomial infection control measures were implemented during the second sample collection period. The toxin gene was amplified by PCR and sequenced for identification. Minimum inhibitory concentration (MIC) of metronidazole, vancomycin, clindamycin, moxifloxacin, rifaximin, fidaxomicin and linezolid were determined using agar double dilution method. We analyzed the drug resistance characteristics of Clostridium difficile and compared the changes of antimicrobial resistance before and after the enhanced control measures implementation. Results All 73 strains tested were sensitive to metronidazole and vancomycin. Resistance rate to clindamycin, moxifloxacin, tetracycline and rifaximin were 79.5%, 26.0%, 27.4%, and 9.5%, respectively. Fidaxomicin and nitazoxanide were highly susceptible in vitro against these strains with MIC ranges <0.008-0.5 mg/L ( P<0.05). Resistance to clindamycin and moxifloxacin were significantly decreased after enhanced control measures implementation (resistance rates were 99.5% vs. 44.8%, 36.4% vs. 10.3%,P<0.05). Additionally, isolate with decreased susceptibility to tinezolid as MIC 16 mg/L was found. Conclusion Clostridium difficileis highly resistant to clindamycin and quinolones. Since strains remain highly sensitive to metronidazole and vancomycin in our hospital, empirical application is reasonable without routine antimicrobial susceptibility testing.
