Tufts University School of Medicine, Boston, MA, USA; Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, AL, USA; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Anaerobe. 2020 Feb;61:102098. doi: 10.1016/j.anaerobe.2019.102098. Epub 2019 Sep 4.
Recurrent Clostridioides (formerly Clostridium) difficile infection (rCDI) is common, and patients who have had one recurrence are more likely to have multiple recurrences. Frequent recurrences have been associated with increased morbidity and mortality, high healthcare costs, and lower quality of life. In this review, we compare the efficacy of interventions designed to prevent rCDI. We performed a systematic review of the English literature, including randomized controlled trials (RCTs) that evaluated rCDI as an outcome. Studies were included irrespective of patient demographics, disease severity, type of intervention, comparator used, or time-point of outcome evaluation. We performed a comprehensive literature search with the assistance of a research librarian. Two reviewers independently extracted data and assessed risk of bias. Our search yielded 38 RCTs (8,102 participants). Nineteen RCTs (3,743 subjects) evaluated antibiotics, eight fecal microbiota transplantation (FMT) (582 subjects), three monoclonal antibodies (MAbs) (2,805 subjects), and eight probiotics, prebiotics, or non-antibiotic polymers (972 subjects). The antibiotic and FMT therapies that demonstrated efficacy in rCDI prevention included: fidaxomicin (when compared to a ten-day vancomycin course) and FMT administered by nasogastric tube (when compared to a fourteen-day vancomycin course and a fourteen-day vancomycin course plus bowel lavage). Actoxumab (MAb against C. difficile toxin A; CDA1) plus bezlotoxumab (MAb against C. difficile toxin B; CDB1) in combination or bezlotoxumab alone appeared to be more effective in preventing rCDI compared to actoxumab alone. Of the prebiotics, probiotics, and nonantibiotic polymers, oligofructose, Saccharomyces boulardii, and the nontoxigenic C. difficile strain M3 were the most efficacious for rCDI prevention. Thirty-eight RCTs (>8,000 participants) evaluating treatment modalities for CDI were examined for efficacy in prevention of rCDI. Several CDI-specific antibiotics, FMT modalities, monoclonal antibodies, and various prebiotics and probiotics demonstrated a reduction in risk of rCDI with the greatest risk reduction observed with FMT and monoclonal antibody therapy. It is notable that the comparators in these studies were very different from one another and the relative risk reduction of rCDI may not be directly comparable from one study to the next.
复发性艰难梭菌（以前称为艰难梭菌）感染（rCDI）很常见，并且已经发生过一次复发的患者更有可能多次复发。频繁复发与发病率和死亡率增加、医疗保健成本高以及生活质量降低有关。在这篇综述中，我们比较了旨在预防 rCDI 的干预措施的疗效。我们对英文文献进行了系统评价，包括将 rCDI 作为结局的随机对照试验（RCT）。无论患者的人口统计学特征、疾病严重程度、干预类型、使用的对照药物如何或结局评估的时间点如何，我们都纳入了这些研究。我们在研究图书馆员的协助下进行了全面的文献检索。两位审查员独立提取数据并评估了偏倚风险。我们的检索结果为 38 项 RCT（8102 名参与者）。19 项 RCT（3743 名受试者）评估了抗生素，8 项粪便微生物群移植（FMT）（582 名受试者），3 项单克隆抗体（MAb）（2805 名受试者）和 8 项益生菌、益生元或非抗生素聚合物（972 名受试者）。在预防 rCDI 方面显示出疗效的抗生素和 FMT 治疗包括：非达霉素（与 10 天万古霉素疗程相比）和通过鼻胃管给予的 FMT（与 14 天万古霉素疗程和 14 天万古霉素疗程加肠道灌洗相比）。抗毒素 A（针对艰难梭菌毒素 A 的 MAb；CDA1）加抗毒素 B（针对艰难梭菌毒素 B 的 MAb；CDB1）联合用药或单独使用抗毒素 B 似乎比单独使用抗毒素 A 更能有效预防 rCDI。在益生元和益生菌以及非抗生素聚合物中，低聚果糖、布拉氏酵母菌和无毒素艰难梭菌菌株 M3 对预防 rCDI 最有效。对 38 项（>8000 名参与者）评估艰难梭菌感染（CDI）治疗方法的 RCT 进行了检查，以评估其预防 rCDI 的疗效。几种艰难梭菌特异性抗生素、FMT 方式、单克隆抗体以及各种益生元和益生菌都显示出 rCDI 风险降低，其中 FMT 和单克隆抗体治疗的风险降低最大。值得注意的是，这些研究中的对照药物彼此非常不同，从一项研究到另一项研究的 rCDI 相对风险降低可能无法直接比较。
