Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile Infection: Systematic Review and Meta-analysis

Abstract

Background Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI. Aim This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI. Methods A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates. Results Two hundred and forty patients from 10 studies (8 case series, 1 case–control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low. Conclusion FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.

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“…Several studies describing the use of FMT for rCDI have since been published, with efficacy reaching 80%-90% (8). FMT is also being used for severe or fulminant CDI, with a 4-week response rate of 88% reported in recent systematic review and meta-analysis (9).…”

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“…In severe-complicated or fulminant CDI (characterized by septic course and/or ileus, toxic megacolon or bowel perforation), early consultation of a surgeon is good clinical practice. In addition, fecal microbiota transplantation (FMT) may be of great value (Song et al 2022 ).…”

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“…The aim of treatment with fecal microbiota transplantation (FMT) is to restore dysbiosis of the gut microbiota, potentially not only bacterial, but possibly also viral and fungal, by transferring stool from a healthy donor to a patient. The effect of FMT in medically severe, recurrent and refractory Clostridium difficile infection is effective and well documented (112,113) and FMT is emerging as a feasible treatment to induce remission in active UC based on several RCTs (114)(115)(116)(117)(118).…”