Treatment of relapsing or recurrent Clostridium difficile infection with frozen, orally administered capsules containing a solution of fecal matter from healthy unrelated donors had promising results, with diarrhea resolving in 90% of patients after one or two rounds of treatment.
“We demonstrated the feasibility of oral administration of frozen encapsulated fecal material from unrelated donors to treat patients with recurrent [Clostridium difficile infection (CDI)],” concluded Dr. Ilan Youngster, of the division of infectious diseases at Massachusetts General Hospital, Boston, and his associates. While the study was limited by the small number patients (20) and the lack of a placebo or comparator group, “if reproduced in future studies with active controls, these results may help make FMT accessible to a wider population of patients, in addition to potentially making the procedure safer.”
The study was published Oct. 11 in JAMA, in conjunction with its presenation at ID Week 2014 (doi:10.1001/jama.2014.13875)
Instead of the most common type of fecal microbiota transplantation (FMT) procedures, which use a suspension of fresh stool from donors related to the patient to reconstitute the normal flora, this feasibility study evaluated the safety and effectiveness of FMT with fecal matter from unrelated, carefully screened healthy donors, which was processed into a solution that was placed into small capsules and then frozen.
The study enrolled 20 patients whose mean age was 64.5 years (one patient was aged 11, the rest were aged 17-89) between August 2013 and June 2014 at Massachusetts General. Patient had had at least three episodes of mild to moderate CDI and failed treatment with vancomycin, with or without an alternative antibiotic; or had been hospitalized with at least 2 episodes of severe CDI.
After one round of treatment with 15 capsules over 2 days, diarrhea resolved (defined as fewer than three bowel movements over 24 hours) in 14 of the 20 patients (70%); at 8 weeks, they remained symptom free. The remaining 6 patients were treated again, a mean of 7 days after the first treatment, and diarrhea resolved in 5. One of the 5 patients relapsed within the 8 week follow-up period, so the overall rate of diarrhea resolution at 8 weeks was 90%.
Overall health score before treatment was the only factor significantly associated with treatment response. Those who required a second treatment had more symptoms and had lower health scores before treatment than those who responded to the first treatment.
The number of daily bowel movements dropped from a median of five per day before treatment to a median of 2 at day 3, and one at 8 weeks, both statistically significant reductions from baseline. Patients also felt better, reflected in improvements in scores on health questionnaires evaluating overall and gastrointestinal health.
There were no cases of vomiting or aspiration and no serious adverse events were observed, Dr. Youngster said. Six patients experienced abdominal cramping and bloating after treatment, which were considered to be treatment related, but resolved.
The 90% clinical resolution rate with this treatment are comparable those in case studies and a randomized study using fresh stool preparations to treat CDI, Dr. Youngster said. “Larger studied are needed to confirm these results and to evaluate long-term safety and effectiveness.
The study was funded with internal hospital division funds. One author is a recipient of a research award sponsored by Seres Health, Cambridge, Mass., for an unrelated clinical trial of a C. difficile colitis treatment. No other author disclosures were reported.