Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam, The Netherlands; Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, The Netherlands.
Clin Microbiol Infect. 2018 May;24(5):452-462. doi: 10.1016/j.cmi.2017.12.022. Epub 2018 Jan 6.
Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, both in healthcare facilities and in the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI.
To review novel treatments and approaches for CDI, except probiotics and vaccines. We focused on new antibiotics, antibiotic inactivators, monoclonal antibodies and gut microbiota modulating therapies.
A literature review was performed for clinical trials published in PubMed, Embase or Cochrane Library between January 2013 and November 2017.
We analysed 28 clinical trials and identified 14 novel agents. Completed phase 2 studies were found for cadazolid, LFF571, ridinilazole and nontoxigenic C. difficile strains. Four phase 3 active comparator studies comparing vancomycin with bezlotoxumab, surotomycin (n = 2) and rifaximin have been published. Seven clinical trials for treatment of multiple recurrent CDI with faecal microbiota transplantation were analysed, describing faecal microbiota transplantation by upper or lower gastrointestinal route (n = 5) or by capsules (n = 2).
Metronidazole is mentioned in the ESCMID guideline as first-line therapy, but we propose that oral vancomycin will become the first choice when antibiotic treatment for CDI is necessary. Fidaxomicin is a good alternative, especially in patients at risk of relapse. Vancomycin combined with faecal microbiota transplantation remains the primary therapy for multiple recurrent CDI. We anticipate that new medication that protects the gut microbiota will be further developed and tested to prevent CDI during antibiotic therapy.
艰难梭菌是医疗保健机构和社区中抗生素相关性腹泻的主要原因。艰难梭菌感染（CDI）的复发率仍然很高，高达 20%。自 2014 年欧洲临床微生物学和传染病学会（ESCMID）发布 CDI 治疗指南以来，已经开发并测试了新的治疗方法，以实现 CDI 的更高持续临床治愈率。
综述除益生菌和疫苗外治疗 CDI 的新方法。我们重点关注新抗生素、抗生素失活剂、单克隆抗体和肠道微生物群调节疗法。
对 2013 年 1 月至 2017 年 11 月期间在 PubMed、Embase 或 Cochrane 图书馆发表的临床试验进行了文献回顾。
我们分析了 28 项临床试验，确定了 14 种新的药物。已完成卡他唑利德、LFF571、里迪尼唑和非产毒艰难梭菌株的 2 期研究。发表了 4 项比较万古霉素与 bezlotoxumab、苏罗替莫和利福昔明的 3 期活性对照研究。分析了 7 项关于粪便微生物群移植治疗多次复发性 CDI 的临床试验，描述了通过上消化道或下消化道途径（n=5）或通过胶囊（n=2）进行粪便微生物群移植。
ESCMID 指南中提到甲硝唑是一线治疗药物，但我们建议在需要 CDI 的抗生素治疗时，口服万古霉素将成为首选。非达霉素是一个很好的替代药物，特别是在有复发风险的患者中。万古霉素联合粪便微生物群移植仍然是治疗多次复发性 CDI 的主要方法。我们预计，将进一步开发和测试保护肠道微生物群的新药，以防止抗生素治疗期间发生 CDI。
