Fecal microbiota transplant effective for recurrent C. difficile infection

Last Updated: 2016-08-24

By Will Boggs MD

NEW YORK (Reuters Health) - Fecal microbiota transplantation (FMT) effectively treats recurrent Clostridium difficile infection (CDI), according to results from the first randomized, double-blind, placebo-controlled trial of this treatment.

FMT aims to restore the normal composition of gut microbiota and is recommended when antibiotics failed to clear the infection. Evidence from case series and open-label clinical trials suggests cure rates of 81% to 100% in recurrent CDI.

Dr. Colleen R. Kelly of Warren Alpert Medical School of Brown University in Providence, Rhode Island, and colleagues examined cure rates and adverse events between donor FMT and autologous FMT (given as the placebo) in 46 patients who had at least three CDI recurrences.

Twenty of 22 patients (90.9%) in the donor FMT group achieved clinical cure, compared with 15 of 24 (62.5%) in the autologous FMT group (p=0.042), the team reports in Annals of Internal Medicine, online August 23.

"It was surprising that many patients reached cure after treatment with placebo," Dr. Kelly told Reuters Health by email. "This was a double-blind study, so I didn't know what treatment I was administering. There were several patients who made a very rapid and dramatic recovery and who I was sure must have received donor FMT. When we unblinded the study at the end, I learned that these patients had actually been treated with their own stool."

Clinical failure occurred a mean of 10 days after the procedure. One of the two patients in the donor-FMT group who failed to maintain a cure was retreated using a different donor and was subsequently cured. The other clinical failure in the donor FMT group was lost to follow-up.

All nine patients who had recurrence after autologous FMT were treated after the trial with donor FMT and remained free of further CDI, resulting in an overall cure rate after a single donor FMT of 93.5%.

"None of the patients from the study have developed a recurrence of C. difficile to date and none have contacted me to ask which treatment arm they received," Dr. Kelly said. "I think they are just happy to be well again."

"FMT is indicated after a 3rd recurrence of CDI (and failure of a tapering/pulse dose regimen of vancomycin)," she said. "However, if a patient has suffered more severe C. diff. episodes (requiring ICU stay, for example), most would offer FMT after a second episode."

"This was a difficult study to do, as patients were often resistant to enrolling in a trial where they might not get a real FMT," Dr. Kelly added. "We used a different donor for each patient, and relied on fresh stool, which presented obvious logistical issues. I am grateful to all the patients and donors who participated and helped us show that FMT is, indeed, an effective therapy for recurrent C. difficile infection."

She also noted that, "Given the limits of the PCR-based testing (which may remain positive after successful treatment), it is important to consider other possible etiologies of diarrhea, such as IBS, which is common after C. difficile infection."

Several outside experts welcomed the new findings.

Dr. Elizabeth L. Hohmann from Massachusetts General Hospital in Boston, who wrote a linked editorial, told Reuters Health by email, "FMT does work; it's not a panacea and still requires further study, especially if envisioned for other illnesses, GI and other. The gut microbiome is a new 'organ' that we need to study."

"I do think it is very important to note that these people in this study were likely a lot less sick and younger than the average person with recurrent CDI," she added.

"I believe it is important to advise patients, especially the young, of the unknowns," Dr. Hohmann concluded. "I have little worry about doing FMT in people in their 70's with 3 episodes of C. diff. and hospitalizations. I proceed more cautiously in young patients and children, though there are some of those who benefit significantly, too."

Dr. Karin Moelling from the University of Zürich, Switzerland, said the new work shows the treatment "is real medicine, not just alternative medicine."

"At this point only patients with 3 or more documented CDI recurrences were studied," she told Reuters Health by email. "We need more studies to find out whether a patient should be treated as early as after a first CDI, e.g., after a hospital infection."

Dr. Colleen S. Kraft from Emory University Hospital in Atlanta, Georgia, observed that, "Recurrent C. difficile is an indication of persistent dysbiosis, and continuing to give antibiotics for treatment becomes a vicious cycle of not being able to restore the microbiota. FMT should be used when individuals enter this cycle of recurrence."

"A 'holy grail' in the field would be the characterization of donor stool that is efficacious - that we could predict what may be curative," Dr. Kraft, who has also studied FMT, told Reuters Health by email. "This would lead to the development of non-feces based microbiota therapies for C. difficile and other diseases."

Dr. Lawrence J. Brandt from Albert Einstein College of Medicine in the Bronx, New York, who has used FMT as a treatment since 1999, told Reuters Health by email, "Stool is now viewed not as a waste product but as a complex and dynamic community of living organisms that may represent a whole new therapeutic armamentarium."

SOURCE: http://bit.ly/2bf2Gs7 and http://bit.ly/2bF3rc3

Ann Intern Med 2016.