New findings published in JAMA suggest that fecal microbiota transplantation via oral capsules is noninferior to delivery by colonoscopy in preventing recurrent Clostridium difficile infection.
According to Dina Kao, MD, FRCPC, associate professor in the division of gastroenterology at the University of Alberta in Edmonton, Canada, and colleagues, fecal microbiota transplantation (FMT) is the most effective therapy to re-establish normal gut bacteria in patients with recurrent C. difficile infection (RCDI), with a success rate between 60% and 90% after just one treatment.
To test the hypothesis that FMT by oral capsule is noninferior to delivery by colonoscopy, Kao and colleagues enrolled 116 patients in Edmonton and Calgary with at least three documented episodes of CDI. They randomly assigned patients to receive one of the two therapies between October 2014 and September 2016 and followed them through the end of 2016.
Following antibiotic treatment with vancomycin, patients who were randomly assigned to the capsule group swallowed 40 capsules under direct observation, and those in the colonoscopy group received 360 mL of fecal slurry via colonoscopy. The primary outcome was the proportion of patients without RCDI 12 weeks after transplant.
Fifty-seven patients in the capsule group and 59 in the colonoscopy group completed the trial. According to Kao and colleagues, in the per-protocol analysis, prevention of RCDI after a single treatment was achieved in 96.2% of patients in both groups (1-sided 95% CI, –6.1% to infinity; P < .001). Rates of minor adverse events were 5.4% in the capsule group compared with 12.5% in the colonoscopy group, and there was no significant difference in improvement in quality of life.
Moreover, Kao and colleagues reported that 66% of participants in the capsule group rated their experience as “not at all unpleasant” compared with 44% of patients in the colonoscopy group (95% CI, 3% to 40%; P = .01)
According to the researchers, most patients with RCDI are referred to gastroenterology or infectious disease departments, where the method and route of FMT delivery may differ.
“Although colonoscopy delivery is more invasive, resource intensive, costly, and inconvenient for patients, it has the advantage of identifying alternative diagnoses,” Kao and colleagues wrote. “Conversely, when FMT is given by oral capsules, it can be administered in an office setting, which could substantially reduce cost and wait time. Complete economic evaluations are needed to understand the value and efficiency of FMT by oral capsule.”
According to Kao and colleagues, their success rate with FMT capsules was higher compared with that in other studies. In a related editorial, Preeti N. Malani, MD, MSJ, professor in the division of infectious diseases at the University of Michigan Medical School, and colleagues called the findings “encouraging.”
But Malani and colleagues also noted contradictory findings from numerous trials exploring FMT for CDI and said further research is needed to determine “the optimal timing and format of FMT, as well as the role for rational design of defined microbial consortia.”
“While it is encouraging that capsules appear to be a viable delivery route for FMT, a number of additional approaches still deserve consideration in future research. These include vancomycin tapers with and without ‘chasers’ of [Dificid (fidaxomicin, Merck)]/[Xifaxan (rifaximin, Salix)], defined microbial communities and sterile fecal-derived products,” they wrote. “If these latter approaches prove to be effective, they may supplant standard FMT and other undefined microbial consortia, making even convenient, capsule-based FMT a tough pill to swallow.”