Fecal microbiota transplantation for treatment of recurrent C. difficile infection: An updated randomized controlled trial meta-analysis

Abstract

ObjectivesAlthough systematic evaluation has confirmed the efficacy of fresh fecal microbiota transplantation (FMT) for treatment of recurrent and/or refractory and/or relapse C. difficile infection (RCDI), it lacks the support of well-designed randomized controlled trials (RCTs), and the latest guidelines do not optimize the management of FMT. In this paper, we focus on an in-depth study of fresh FMT and fecal infusion times to guide clinical practice.MethodsWe reviewed studies in PubMed, Medline, Embase, the Cochrane library and Cochrane Central written in English. The retrieval period was from the establishment of the databases to September 20th, 2018. The retrieval objects were published RCTs of RCDI treated by fresh FMT. The intervention group was fresh FMT group, while the control group included antibiotic therapy or placebo or frozen FMT or capsule. The primary and secondary outcomes were the clinical remission of diarrhea without relapse after 8–17 weeks and the occurrence of severe adverse events, respectively. Subgroup analysis analyzed the effect of single and multiple fecal infusions. Two authors independently completed the information extraction and assessed risk of bias and overall quality of the evidence.Results8 randomized controlled trials met the inclusion criteria, involving 537 patients (273 in the fresh FMT group and 264 in the control group). The recurrence rate of clinical diarrhea in the fresh FMT group was 11.0% (30/273), which was significantly lower than the control group (24.6%, 65/264; P < 0.05); the pooled relative risk (RR) was 0.38 (95%CI:0.16–0.87; I2 = 67%; P = 0.02) in the fresh FMT group, and the clinical heterogeneity was significant and random effects model was used; However, there was no significant difference neither for the effect of antibiotic treatment/frozen feces transplanted by enema (RR = 1.07; 95%CI: 0.64–1.80; I2 = 0%; P = 0.79) or capsule/frozen feces transplanted by colonoscopy (RR = 0.42; 95%CI: 0.05–3.94; I2 = 43%; P = 0.45) compared with fresh FMT. The subgroup analysis showed that FMT by multiple infusions could effectively and significantly (RR = 0.24; 95%CI:0.10–0.58; I2 = 0%; P = 0.001) improve the clinical diarrhea remission rate. Most mild to moderate adverse events caused by FMT were self-limited and could be quickly alleviated; no severe adverse events happened because of FMT.ConclusionsOverall, the use of fresh feces for bacterial transplantation was the best efficiency for RCDI compared to antibiotic therapy or placebo. The fecal transmission method by enema was not ideal, but capsules or frozen feces transported by colonoscopy could be an alternative treatment compared to fresh FMT. For patients with severe RCDI, multiple fecal transplants can effectively improve their diarrhea remission rate. The focus of future research should be on how to standardize the production of capsules or frozen feces to better guide the clinical management of RCDI patients by FMT.

Fecal microbiota transplantation ameliorates active ulcerative colitis

“…It is not clear whether fresh or frozen-thawed microbiota improves the efficiency of FMT; however, frozen-thawed microbiota is a more convenient method (36,37). Hamilton et al (38) reported the successful use of standardized, partially purified and frozen fecal microbiota to treat C. difficile infection.…”

Insights into the Role of Human Gut Microbiota in Clostridioides difficile Infection

“…The number of concurrent infections required to conduct fecal transplantations has not been clearly defined. However, recent evidence includes cases of patients with three or more incidents of CDI despite appropriate treatment, or two or more incidents of CDI with hospitalization and significant morbidity, patients with moderate CDI irresponsive to treatment with oral vancomycin for over a week, or patients with severe CDI irresponsive to oral vancomycin for 48 hours [110][111][112]. In a randomized study, 93% of the patients that received oral vancomycin and bowel irrigation followed by FMT exhibited a significant decrease in their diarrheal episodes, whereas only 31% of the patients that received only vancomycin and 23% of those who received vancomycin and bowel irrigation had positive outcomes, demonstrating that FMT was significantly more effective for the treatment of recurrent C. difficile infection than the use of vancomycin [113].…”

Proton pump inhibitor in upper gastrointestinal fecal microbiota transplant: A systematic review and analysis

“…Second, the effect of pre‐procedural PPIs on multiple infusion FMT was not studied. Numerous trials have shown impressive efficacy of FMT with multiple infusions, approaching 93–100% . For this review, we defined our inclusion criteria to include only first infusion data to allow for comparison of the primary and secondary endpoints and minimize confounding factors.…”