Treating recurrent Clostridium difficile infections with donor feces resulted in better treatment outcomes than vancomycin, particularly for patients with multiple relapses, a study found.
The study enrolled adults who had a relapse of C. difficile infection after at least one course of adequate antibiotic therapy, recurring diarrhea and a positive stool test for C. difficile toxin, from patients at the Academic Medical Center in Amsterdam. Patients were randomly assigned in an open-label, controlled trial to receive donor feces, vancomycin or vancomycin and bowel lavage from January 2008 through April 2010.
Results appeared online Jan. 16 at the New England Journal of Medicine.
Although researchers originally intended to enroll 40 patients per study group, most patients in both control groups relapsed and a safety monitoring board recommended ending the trial.
Of 16 patients in the donor feces group, 13 (81%) were cured after the first infusion. Three remaining patients received a second fecal donation from a different donor. Two were subsequently cured, for an overall cure rate of 94%.
Resolution occurred in 4 of 13 patients (31%) in the vancomycin-alone group and in 3 of 13 patients (23%) in the vancomycin with bowel lavage group. The overall cure rate ratio of the fecal infusion patients was 3.05 as compared with vancomycin alone (99.9% confidence interval [CI], 1.08 to 290.05) and 4.05 as compared with vancomycin with bowel lavage (99.9% CI, 1.21 to 290.12).
During follow-up, 14 cured patients reported diarrhea. The episodes were short and self-limited in 10 patients. Three other patients returned to their pre-infection baseline of at least three stools per day and had no clinical suspicion of recurrence. One patient who'd responded to treatment of vancomycin-only continued to have persistent diarrhea but with repeatedly negative toxin tests. Researchers maintained a clinical suspicion of recurrence.
Eighteen patients who had a relapse after initial antibiotic treatment received off-protocol donor-feces infusions; of these patients, 15 (83%) were cured. Eleven patients were cured after one fecal transplant, and 4 patients were cured after a second infusion.
Researchers wrote, "Although our study was designed for patients with any recurrence of C. difficile infection, only 8 of 43 patients were included after a first relapse, reflecting the reluctance of patients and physicians to choose donor-feces infusion at an early stage. The efficacy of antibiotic therapy decreases with subsequent recurrences, and it seems reasonable to initiate treatment with donor-feces infusion after the second or third relapse."
A review, published by Lawrence J. Brandt, MD, FACP, separately in the American Journal of Gastroenterology on Jan. 15, concluded that, "There is a conceptual sea change that is developing in our view of bacteria from their role only as pathogens to that of being critical to health maintenance in a changing world. Future studies are certain to narrow the spectrum of organisms that need to be given to patients to cure disease. FMT (fecal microbiota transplantation) is but the first step in this journey."
C. diff. recurs in 10–20% of patients after initial antibiotic therapy and up to 40–65% in patients who are retreated for a second episode, Dr. Brandt wrote. Fecal transplants likely correct the imbalance by restoring normal gut flora, compared to antibiotic treatment, "which, in a sense, perpetuates the very condition that lead to the initial episode of CDI (C. diff infection), namely an altered intestinal microbiome."
After outlining a step-by-step procedure, Dr. Brand outlines how many other conditions can be aided by fecal transplants. He writes, "I believe it also has a role as first-line treatment for patients with CDI rather than antibiotics because of its rapid effect, minimal risk, relatively low cost and reestablishment of a 'balanced' colonic microbiota.
"I, and others, also have used FMT to treat patients with severe CDI manifest by toxic megacolon or ileus and have seen the patient's, family's, gastroenterologist's, and even surgeon's relief as the patient's abdominal distention, fever and white blood cell count decreased, occasionally within hours of the procedure; in none of these cases was the patient's condition or course of disease worsened by FMT."