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Fecal transplantation not superior to vancomycin for recurrent C. difficile
Vancomycin followed by a single fecal transplantation via enema was not significantly more effective than tapered-dose oral vancomycin for recurrent Clostridium difficile infection, researchers in Canada found. Based on the results of a futility analysis, the study was terminated early after interim analysis.
The researchers suggest that further research would be necessary for optimal timing, number of administrations and donor selection to make fecal transplantation a viable treatment for recurrent C. difficile.
“Fecal transplantation … is a promising salvage therapy for recurrent C. difficile infection,” Susy S. Hota, MD, MSc, of the department of infection prevention and control, University Health Network, Toronto, and colleagues wrote. “Five randomized trials have shown symptom resolution in 70% to 94%; however, none of these studies compared fecal transplantation to standard of care treatment and not all evaluated fecal transplantation for treatment of active episodes of recurrent C. difficile infection. Therefore, the true effectiveness of fecal transplantation, as compared to current standard of care, for treatment of an acute episode of recurrent C. difficile infection remains uncertain.”
The researchers performed a stage 2/3 single-center, open-label trial on 30 patients from the province of Ontario who experienced a recurrence of C. difficile infection. Patients were randomly assigned to 6-week vancomycin taper (n = 14) or 14 days of oral vancomycin plus a 500 mL fecal transplantation enema (n = 16).
Two patients in the vancomycin group left the study: one due to non-adherence, and one to seek fecal transplantation elsewhere. Most patients were women and had experienced four or five episodes of C. difficile before the trial, the researchers wrote. Thirteen participants in the fecal transplantation group and 10 in the vancomycin group had experienced vancomycin failure at least once. Follow-up was 120 days.
The trial was terminated after interim analysis because a futility analysis “did not support continuing the study,” Hota and colleagues wrote. Nine patients (56.2%) in the fecal transplantation group experienced a recurrence of C. difficile, along with five (41.7%) in the vancomycin group. Nearly half (43.8%) of the fecal transplantation group experienced symptom resolution, compared with 58.3% in the vancomycin group.
“We show a similar recurrence rate in recurrent C. difficile infection patients treated with 14 days oral vancomycin followed by single fecal transplantation by enema compared with oral vancomycin taper,” the researcher wrote. “These data should be taken into consideration in C. difficile infection treatment guidelines and in the design of fecal transplantation programs. More research is needed to optimize fecal transplantation methodologies — specifically, donor selection, fecal transplantation manufacturing, timing, route and number of administrations.”
In an accompanying editorial, Dale N. Gerding, MD, and Stuart Johnson, MD, both of Loyola University Chicago Stritch School of Medicine, wrote that fecal microbiota transplantation “should be administered as part of a well-designed clinical trial that includes definition of the fecal microbiota transplantation dosing schedule, or should be reserved for patients who cannot be managed with appropriate antibiotic management.
“In the meantime, we have additional evidence of the efficacy of vancomycin taper/pulse administration as an effective treatment,” they wrote. – by Andy Polhamus
Disclosure: Hota reports receiving a grant and honoraria from Cubist (Merck) pharmaceuticals. Gerding reports fees from Acetelion, DaVolterra, Merck, MGB, Pfizer, Rebiotix, Sanofi Pasteur, Seres Therapeutics and Summit Therapeutics. Johnson reports fees from Bio-K+, Seres Therapeutics and Summit Therapeutics. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.
