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Donor FMT safe, superior to autologous transplant for treating recurrent C. difficile
Colonoscopic fecal microbiota transplantation appeared to more effectively prevent recurrent Clostridium difficile infection when developed from the stool of a healthy donor, as opposed to the patient’s own, according to a recently published double-blind trial.
In addition, the transplant restored the diversity and composition of CDI patients’ bacterial community and resulted in no serious adverse events, according to Colleen R. Kelly, MD, gastroenterologist at the Women’s Medicine Collaborative and assistant professor of medicine at the Warren Alpert Medical School of Brown University, and colleagues.
“The evidence for [fecal microbiota transplantation (FMT)] rests largely on case series and several open-label clinical trials that have suggested cure rates of 81% to 100% in recurrent CDI,” the researchers wrote. “To date, there has not been an adequately controlled and blinded trial of FMT for CDI treatment. Furthermore, the optimal method for administering FMT has not been determined.”
Colleen R. Kelly
To further explore FMT, Kelly and colleagues enrolled recurrent CDI patients receiving care from an academic medical center in New York and another in Rhode Island. Patients were eligible for inclusion if they had at least three recurrences, vancomycin treatment for their most recent episode and no other complicating conditions or prior FMT. The researchers randomly assigned these participants (n = 46) to receive stool from a healthy donor or a self-supplied sample collected before treatment, delivered via colonoscopy. Kelly and colleagues monitored patients for diarrhea or adverse events, and compared outcomes between the study arms.
The researchers assigned patients to receive donor (n = 22) or autologous (n = 24) stool. Patients treated with donor FMT (90.9%; 95% CI, 69.2-97.8) demonstrated superior cure rates than those receiving autologous FMT (62.5%; 95% CI, 41.6-79.6). Autologous patients at the center in New York achieved clinical cure nearly as often as those in the donor arm (90% vs. 91.7%), although there was no significant interaction between study sites. Clinical failures occurred a mean of 10 days after FMT, and all autologous patients whose FMT failed were able to halt recurrence with a subsequent donor stool transplant. One patient in the donor arm and three in the autologous arm experienced a serious adverse event; none, however, was related to FMT. The microbial diversity and community structure of donor FMT patients alone was restored after treatment, with reductions in Proteobacteria and Verrucomicrobia and increases in Bacteroidetes and Firmicutes.
Elizabeth L. Hohmann
“FMT using fresh donor stool administered via colonoscopy after a course of vancomycin was effective at preventing further CDI episodes in patients with multiply recurrent infection,” Kelly and colleagues wrote. “Differences in efficacy between sites suggest that some patients with lower risk for CDI recurrence may not benefit from FMT. Further research may help determine the best candidates for FMT.”
In an editorial reviewing the trial’s findings, Elizabeth L. Hohmann, MD, chair and physician director of the Partners Human Research Committees and associate professor of medicine at Massachusetts General Hospital, explored the “striking” differences between the recurrence rates of autologous FMT patients at separate study sites. Based on patient characteristic data, she suggested that the discrepancy may have been due to more extensive administration of suppressive antibiotics or the presence of other nontoxigenic organisms, and noted how these and other findings from the study highlight the gaps remaining in microbiome knowledge.
“Rigorous controlled trials are valuable even when we think we know the answer,” she wrote. “Their results prompt us to ask again whether microbial manipulation has any as-yet unappreciated health benefits or risks and whether there are preferred microbiomes for specific human populations or locales.” – by Dave Muoio
Disclosure: Kelly reports relationships with Assembly Biosciences and Seres Health outside of the current study. Please see the full study and editorial for a list of Hohmann and all other researchers’ relevant financial disclosures.