In a recent study published in the Cochrane Database of Systematic Reviews, researchers provide an overview of fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI).
Study: Fecal microbiota transplantation for the treatment of recurrent Clostridioides difficile (Clostridium difficile). Image Credit: Prrrettty / Shutterstock.com
C. difficile, a bacterial organism, may repeatedly cause potentially fatal diarrhea upon infecting individuals with microbial dysbiosis. The conventional approach to treating CDI includes antibiotics, which could further aggravate intestinal microbial alterations.
FMT can also be used to manage CDI by restoring the balance of the gut microbiome. Nevertheless, further research, including randomized controlled trials (RCTs), is needed to assess the risk-benefit ratio of FMT concerning rCDI management.
About the study
In the present systematic review, researchers review existing data on FMT as a management option for rCDI in comparison to conventional treatment approaches, including antibiotics.
The team used standard and extensive Cochrane methods for searching relevant data until March 31, 2022. Only RCTs, including pediatric and/or adult rCDI patients, provided interventions that satisfy the FMT criteria, which involves administering donor feces from the distal intestinal microbiome into the gastrointestinal (GI) tract of rCDI patients, were included.
Other treatment groups included those who received placebo therapies, no therapeutic intervention, autologous FMT, or antibiotics to treat CDIs.
The primary study outcomes were the percentage of individuals with cDI resolution and serious-type adverse events. Secondary study outcomes included treatment failure, any‐cause deaths, withdrawal from the study, the recurrence rate of CDI infections following FMT, adverse events, life quality, and colectomy rates.
The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. The Risk of Bias 2 (RoB 2) tool was used to assess bias risks in the included studies. Additionally, the risk ratios (RR) and number needed to treat for an additional beneficial outcome (NNTB) were calculated.
A total of six RCTs were considered for the final review, which consisted of 320 adult individuals. These trials were conducted in several countries, including Italy, Denmark, the Netherlands, the United States, and Canada.
Four RCTs were performed at a single center, whereas two RCTs were performed at multiple centers. Only one RCT included immunocompromised individuals who were distributed evenly between the intervention (FMT) and comparator (non-FMT) groups.
In one RCT, FMT was administered through the upper GI tract using nasoduodenal tubes. Comparatively, two RCTs involved enema administration of FMT, and another two involved colonoscopic FMT administration. In one RCT involving colonoscopic or nasojejunal delivery of donor fecal matter, the choice of administration was based on an individual’s colonoscopic tolerance.
Five records included one or more comparison groups receiving vancomycin. Bias risks were not high for any of the study outcomes.
The safety and efficacy of FMT in treating rCDI were assessed in all included RCTs. Pooled data from all studies indicated that FMT was likely to increase rCDI resolution among immunocompetent individuals as compared to controls.
RR and NNTB values were 1.9 and 3.0, respectively. The quality of evidence was considered to be moderate in the included studies.
Importantly, FMT led to a marginal decrease in serious adverse events; however, these observations were associated with wide confidence interval (CI) estimates, including RR and NNTB values of 0.7 and 12, respectively, thus indicating a moderate-level certainty of this evidence.
Any-cause mortality counts, which were evaluated from only a few events, were reduced following FMT, with RR and NNTB values of 0.6 and 20, respectively. The certainty of the evidence was low for this finding.
The rates of colectomy were not documented in any of the RCTs. Eliminating the RCT that included immunosuppressed individuals yielded similar findings.
Based on these findings, among immunocompetent and adult rCDI patients, FMT is more likely to resolve rCDI than alternative therapies, including antibiotics. Only a few adverse events and any-cause deaths were reported; therefore, conclusive evidence on FMT safety could not be obtained.
Further research, including the analysis of data documented in large-scale and nationwide registries, is needed to evaluate the acute and chronic risks associated with FMT administration among rCDI patients. Future studies must also evaluate the therapeutic effects of FMT among immunosuppressed individuals to devise health policies and strategies accordingly and prioritize individuals who are most likely to benefit from the therapy.