Head-to-Head Comparison of Treatments for Recurrent C difficile Infection

A recent Bayesian network meta-analysis (NMA) assessed the efficacy of various treatments for recurrent Clostridioides difficile infection (rCDI) using data from 17 randomized controlled trials involving 4,148 patients. The analysis found that fecal microbiota transplantation (FMT) via the lower gastrointestinal (LGI) route was the most effective treatment for rCDI.¹

FMT by LGI showed an odds ratio (OR) of 32.33 (95% CI: 4.03, 248.69) compared to placebo. FMT via the upper gastrointestinal (UGI) route also showed significant efficacy, though the difference between LGI and UGI was not statistically significant (OR: 1.72, 95% CI: 0.65, 5.21). In the ranking analysis, FMT by LGI was ranked first, followed by FMT by UGI.¹

Other treatments evaluated in the study, including vancomycin, fidaxomicin, vancomycin plus FMT, placebo, and monoclonal antibodies, were found to be less effective for rCDI. Antibiotics like vancomycin and fidaxomicin showed lower efficacy, possibly due to their impact on the gut microbiota. New microbiota-based therapies, such as Vowst (SER109) and Rebyota (RBX2660), showed some potential but require further investigation.¹

According to the investigators, “FMT was the most effective in rCDI patients. It is recommended as the best treatment option for rCDI after antibiotic failure. There is also a large amount of evidence pointing to the effectiveness of FMT.”¹

To include, the investigators ranked the treatments based on their effectiveness in treating rCDI and the safety profiles of each therapy, as supported by the evidence discussed.¹

1. FMT (LGI route)

2. FMT (UGI route)

3. Vowst

4. Rebyota

5. Fidaxomicin

6. Autologous FMT (AFMT)

7. Monoclonal Antibodies (Bezlotoxumab)

8. Vancomycin/Placebo

The study highlighted concerns with FMT, including the lack of standardized, FDA-compliant manufacturing processes, which may affect the safety and consistency of the procedure. Despite these concerns, the NMA supports further research into microbiota-based therapies for rCDI.¹

In contrast, Contagion recently reported a randomized controlled trial (RCT) involving 153 patients with rCDI tested capsule-delivered FMT against a placebo. The trial found no significant difference between the groups, with 32.9% of FMT patients and 29.9% of placebo patients experiencing recurrence or death within 56 days. The trial was stopped early due to futility, indicating that capsule-delivered FMT did not provide a benefit over placebo.²

While the NMA supports the efficacy of FMT, particularly when delivered via the LGI route, the RCT showed no benefit to capsule-delivered FMT and was halted. These differing results highlight the importance of factors such as delivery method, patient selection, and standardization in FMT administration. These studies suggest that additional research is needed to improve treatment strategies for rCDI, including more clinical trials to assess the effectiveness, safety, and long-term outcomes of FMT and other microbiota-based treatments.

Learn more about FMT from experts in our recent peer exchange: Preventing Recurrent Clostridioides difficile Infections with Fecal Microbiota-Based Therapies

References

1. Duo H, Yang Y, Zhang G, et. al. Comparative effectiveness of treatments for recurrent Clostridioides difficile infection: a network meta-analysis of randomized controlled trials. Frontiers. October 16, 2024. Accessed November 13, 2024. https://doi.org/10.3389/fphar.2024.1430724

2. Drekonja D, Shaukat A, Huang Y, et al. A randomized controlled trial of efficacy and safety of Fecal Microbiota Transplant for preventing recurrent Clostridioides difficile infection, Clinical Infectious Diseases, 2024; ciae467. September 13, 2024. Accessed November 13, 2024. doi: https://doi.org/10.1093/cid/ciae467