Fecal microbiota transplantation by oral capsules is as effective as infusion by colonoscopy for preventing recurrence of C. difficile infection in patients with recurrent infections
EBM Focus - Volume 12, Issue 50
- Fecal microbiota transplantation (FMT) is a potential therapy for Clostridium difficile infection. The optimal mode of delivery has not yet been determined.
- In a non-inferiority trial, 116 adults with recurrent uncomplicated C. difficile infection were randomized to FMT delivered orally in 40 capsules vs. infusion by colonoscopy.
- Delivery of FMT by oral capsules was found to be as effective as infusion by colonoscopy for the prevention of C. difficile infection.
Recurrence of Clostridium difficile infection is estimated to occur in 12-20% of treated patients and in 50-65% of patients who have had ≥ 2 episodes (Cleve Clin J Med. 2006). Recommended therapies for the treatment of recurrent infections include vancomycin (Infect Control Hosp Epidemiol 2010, Clin Microbiol Infect 2016) and fidaxomicin (Clin Microbiol Infect 2016). Fecal microbiota transplantation (FMT) is reported to have high cure rates in a non-comparative analysis (Aliment Pharmacol Ther 2017) and is emerging as a potential treatment for recurrent C. difficile infection. In small randomized trials comparing FMT with vancomycin in patients with recurrent C. difficile, two trials demonstrated greater efficacy with FMT (Aliment Pharmacol Ther 2015, N Engl J Med 2013) and one trial showed no difference in recurrence rates (Clin Infect Dis 2017). The optimal dosing, fecal components, and route of delivery of FMT have not yet been determined. Routes of FMT delivery were compared in a recent non-inferiority trial with 116 adults (mean age 58 years, 68% female) with ≥ 3 episodes of uncomplicated C. difficile infection. The patients were randomized to frozen FMT delivered orally in 40 capsules vs. infusion by colonoscopy (360 mL fecal slurry in cecum). Use of proton-pump inhibitors (PPI) was discontinued after screening. All patients received vancomycin until 24 hours prior to FMT and 4 L polyethylene glycol the night before transplantation. Non-inferiority of oral FMT was defined as a success rate for prevention of recurrent C. difficile infection not more than 15% lower than with colonoscopy FMT.
The per protocol analysis for non-inferiority included 91% of the randomized patients. The success rate for the prevention of recurrent C. difficile infection at 12 weeks was 96.2% in both groups. The lower limit of the 95% CI for the difference between groups was 6.1% indicating that oral delivery was non-inferior to delivery by colonoscopy. The percentage of patients considering the treatment to be “not at all unpleasant” was higher with oral FMT (in 66% vs. 44% with colonoscopy FMT, p = 0.01, NNT 5). There was no significant difference in improvement in quality of life scores at 4 weeks. Adverse effects including nausea, vomiting, fever, or abdominal discomfort occurred in 5.4% with oral FMT vs. 12.5% with colonoscopy FMT (statistical comparison not reported).
Delivery of FMT by the oral route was found to be as effective as delivery via colonoscopy for the prevention of C. difficile infection in patients with recurrent infections. Patients in both groups appear to be amenable to FMT as almost all (97%) stated that they would be willing to undergo the assigned treatment again if necessary. FMT by capsule, however, may be preferred as it was deemed more often “not to be unpleasant” compared to colonoscopy. PPIs and acid-resistant capsules were not used in this trial suggesting that at least with the inoculum used in this study, protection against the effects of acid on the microbiota transplant is not necessary for the oral route of delivery; a promising finding given that PPI use is associated with recurrent C. difficile infection (Infect Control Hosp Epidemiol 2015). Guidance on the use of FMT to treat C. difficile infection refractory to standard therapy is available from the U.S. Food and Drug Administration (FDA 2013) and a more recent guidance document is available in draft form (FDA 2016). In summary, the results of this trial indicate that FMT by the oral route to prevent C. difficile infection in patients having uncomplicated infection recurrences may be a viable option to avoid the risks associated with colonoscopy.