OBJECTIVES: The clinical and economic burden ofClostridium difficileinfection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.
METHODS: An electronic search was conducted using MEDLINE (1946–March 2012), EMBASE (1974–March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups.
RESULTS: Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (CochranQtestP=0.13,I2=33.7%).A priorisubgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69–90%)) (proportion difference of WPR was 10.6% (95% CI −0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years.
CONCLUSIONS: FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated.
1 Division of Gastroenterology, Department of Medicine, McMaster University Health Science Centre, Hamilton, Ontario, Canada
2 Department of Medicine, Division of Infectious Diseases, McMaster University, Hamilton, Ontario, Canada
3 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
4 Hamilton Regional Laboratory Medicine Program, Hamilton, Ontario, Canada
5 Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
Correspondence: Richard H. Hunt, Division of Gastroenterology, Department of Medicine, McMaster University Health Science Centre, Room 4W8A, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5. E-mail: firstname.lastname@example.org
SUPPLEMENTARY MATERIAL accompanies this paper at http://links.lww.com/AJG/A723
Received 21 November 2012; accepted 14 February 2013
published online 19 March 2013