Clostridioides (Clostridium) difficile is an important pathogen of healthcare- associated diarrhea, however, an increase in the occurrence of C. difficile infection (CDI) outside hospital settings has been reported. The accumulation of antimicrobial resistance in C. difficile can increase the risk of CDI development and/or its spread. The limited number of antimicrobials for the treatment of CDI is matter of some concern. In order to summarize the data on antimicrobial resistance to C. difficile derived from humans, a systematic review and meta-analysis were performed. We searched five bibliographic databases: (MEDLINE [PubMed], Scopus, Embase, Cochrane Library and Web of Science) for studies that focused on antimicrobial susceptibility testing in C. difficile and were published between 1992 and 2019. The weighted pooled resistance (WPR) for each antimicrobial agent was calculated using a random- effects model. A total of 111 studies were included. The WPR for metronidazole and vancomycin was 1.0% (95% CI 0–3%) and 1% (95% CI 0–2%) for the breakpoint > 2 mg/L and 0% (95% CI 0%) for breakpoint ≥32 μg/ml. Rifampin and tigecycline had a WPRs of 37.0% (95% CI 18–58%) and 1% (95% CI 0–3%), respectively. The WPRs for the other antimicrobials were as follows: ciprofloxacin 95% (95% CI 85–100%), moxifloxacin 32% (95% CI 25–40%), clindamycin 59% (95% CI 53–65%), amoxicillin/clavulanate 0% (0–0%), piperacillin/tazobactam 0% (0–0%) and ceftriaxone 47% (95% CI 29–65%). Tetracycline had a WPR 20% (95% CI 14–27%) and meropenem showed 0% (95% CI 0–1%); resistance to fidaxomicin was reported in one isolate (0.08%). Resistance to metronidazole, vancomycin, fidaxomicin, meropenem and piperacillin/tazobactam is reported rarely. From the alternative CDI drug treatments, tigecycline had a lower resistance rate than rifampin. The high-risk antimicrobials for CDI development showed a high level of resistance, the highest was seen in the second generation of fluoroquinolones and clindamycin; amoxicillin/clavulanate showed almost no resistance. Tetracycline resistance was present in one fifth of human clinical C. difficile isolates.

中文翻译：

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源自人类的艰难梭菌（Clostridium difficile）的抗菌素耐药性：系统评价和荟萃分析

艰难梭菌（Clostridium difficile）是医疗保健相关性腹泻的重要病原体，然而，据报道，在医院环境外，艰难梭菌感染 (CDI) 的发生率有所增加。艰难梭菌中抗菌素耐药性的积累会增加 CDI 发展和/或其传播的风险。用于治疗 CDI 的抗菌药物数量有限，这引起了一些关注。为了总结来自人类的艰难梭菌抗微生物药物耐药性的数据，进行了系统评价和荟萃分析。我们检索了五个书目数据库：（MEDLINE [PubMed]、Scopus、Embase、Cochrane Library 和 Web of Science），以寻找专注于艰难梭菌抗菌药物敏感性测试的研究，这些研究发表于 1992 年至 2019 年之间。使用随机效应模型计算每种抗菌剂的加权合并耐药性 (WPR)。共纳入 111 项研究。甲硝唑和万古霉素的 WPR 为 1.0% (95% CI 0–3%) 和 1% (95% CI 0–2%) 断点 > 2 mg/L 和 0% (95% CI 0%) 断点≥32 μg/ml。利福平和替加环素的 WPR 分别为 37.0% (95% CI 18–58%) 和 1% (95% CI 0–3%)。其他抗菌药物的 WPR 如下：环丙沙星 95% (95% CI 85–100%)、莫西沙星 32% (95% CI 25–40%)、克林霉素 59% (95% CI 53–65%)、阿莫西林/克拉维酸 0% (0–0%)、哌拉西林/他唑巴坦 0% (0–0%) 和头孢曲松 47% (95% CI 29–65%)。四环素的 WPR 为 20%（95% CI 14-27%），美罗培南为 0%（95% CI 0-1%）；在一种分离株中报告了对非达霉素的耐药性 (0.08%)。对甲硝唑、万古霉素、很少报道非达霉素、美罗培南和哌拉西林/他唑巴坦。从替代的 CDI 药物治疗来看，替加环素的耐药率低于利福平。CDI发生的高危抗菌药物耐药性较高，以二代氟喹诺酮类和克林霉素耐药率最高；阿莫西林/克拉维酸盐几乎没有耐药性。五分之一的人类临床艰难梭菌分离株中存在四环素耐药性。阿莫西林/克拉维酸盐几乎没有耐药性。五分之一的人类临床艰难梭菌分离株中存在四环素耐药性。阿莫西林/克拉维酸盐几乎没有耐药性。五分之一的人类临床艰难梭菌分离株中存在四环素耐药性。