Faecal microbiota transplantation for recurrent Clostridioides difficile infection: An updated systematic review and meta-analysis

Abstract

Background: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (CDI), but inconsistent effect rates and uncertain evidence levels have warranted caution. To clarify, we aimed to establish the evidence of FMT for recurrent CDI, updated across different delivery methods, treatment regimens, and in comparison with standard antibiotics.

Methods: In this updated systematic review and meta-analysis, we searched PubMed, Scopus, Embase, Web of Science, Clinical Key, and Svemed+ for FMT literature published in English until November 11, 2019. We included observational and clinical trials with or without antibiotic comparators and excluded studies with below 8 weeks follow-up and fewer than 15 patients. The primary outcome was clinical outcome by week 8. We comprehensively extracted patient and procedural data. In a random-effects meta-analysis, we estimated the clinical effect for repeat or single FMT, different delivery methods, and versus antibiotics. We rated the evidence according to the Cochrane and GRADE methods. The PROSPERO preregistration number is CRD42020158112.

Findings: Of 1816 studies assessed, 45 studies were included. The overall clinical effect week 8 following repeat FMT (24 studies, 1855 patients) was 91% (95% CI: 89-94%, I ²=53%) and 84% (80-88%, I ²=86%) following single FMT (43 studies, 2937 patients). Delivery by lower gastrointestinal endoscopy was superior to all other delivery methods, and repeat FMT significantly increased the treatment effect week 8 (P<0·001). Compared with vancomycin, the number needed to treat (NNT) for repeat FMT was 1·5 (1·3-1·9, P<0·001) and 2.9 (1·5-37·1, P=0·03) for single FMT. Repeat FMT had high quality of evidence.

Interpretation: High-quality evidence supports FMT is effective for recurrent CDI, but its effect varies with the delivery method and the number of administrations. The superior NNT for FMT compared with antibiotics suggests that patients may benefit from advancing FMT to all instances of recurrent CDI.

Funding: Innovation Fund Denmark (j.no. 8056-00006B).

Keywords: CDAD, CD associated diarrhoea; CDI; CDI, Clostridioides difficile infection; CI, Confidence interval; Clostridioides difficile; Clostridioides difficile infection; FMT; FMT, Faecal microbiota transplantation; Fecal microbiota transplantation; GI, Gastrointestinal; Meta-analysis; NA, Not available; NOS, Newcastle-Ottawa quality assessment Scale; Number needed to treat; Number needed to treat, NNT; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analysis; RR, Relative risk; Randomised clinical trial, RCT; RoB2, Cochrane Risk of Bias 2; Systematic review.

Fig. 1

PRISMA flowchart of included and excluded studies.

Fig. 2

The cumulative effect of faecal microbiota transplantation (FMT) week 8 on recurrent Clostridioides difficile infection (CDI) following single and repeated administrations grouped by delivery method. The vertical bars indicate the 95% confidence limits. Abbreviations: GI: Gastrointestinal.

Fig. 3

Forest plots of the week 8 effects for A) single and B) repeat faecal microbiota transplantation (FMT) versus vancomycin (standard and tapered regimens) on recurrent CDI in randomised clinical trials.