The study is the first “head-to-head” comparison of fecal transplants and antibiotic treatments, which are presently the “standard” of care.
A new study published by Canadian researchers in Clinical Infectious Diseases indicates that a single fecal transplant may not be any more effective than oral antibiotics in treating Clostridium difficile infections (CDIs).
Although the study has received some criticism for its methods of administration (the transplant was conducted using a single enema and a relatively large amount of stool), the results are important because the study is the first “head-to-head” comparison of fecal transplants and antibiotic treatments, which are presently the “standard” of care.
Lead researcher Susy Hota, MD, medical director of infection prevention and control at University Health Network in Toronto, explained, “I was struck by how many patients I encountered with recurrent C. difficile infection, and it was so challenging to get them out of the cycle of recurrence. [Our team] felt strongly that there was a need for a well-designed study to address the safety and efficacy [of fecal microbiota transplant(FMT)]. There were so many unknowns about how to do it and how well it truly worked.”
C. difficile infections are most common in the elderly , occurring with some frequency in hospitals and nursing homes. Patients already on antibiotics often contract the infection, and C. difficile spores are particularly problematic in institutional settings because they can live for a long time outside the human body on things like bed linens and rails. Some strains of the bacteria are difficult to treat because they are resistant to a number of antibiotics. A patient with a C. difficile infection may experience diarrhea, fever, loss of appetite, and belly pain and tenderness.
The study compared a regimen of 14 days of oral vancomycin followed by one fecal transplant by enema with a 6-week taper of oral vancomycin. Participants were all experiencing recurrent CDI, and patients with significantly compromised immune systems, histories of fulminant CDI, and irreversible bleeding disorders were excluded from the study. Patients could participate if they had at least two episodes of lab- or pathology-confirmed CDI and had been treated with at least one course of oral vancomycin. The patients were randomized at a 1:1 ratio but the study was not blind, “as it would be impractical due to fecal transplant odor” and since the research ethics board’s refusal to endorse sham enemas, the scientists noted.
A total of 30 patients participated in the study between January 2011 and July 2014. Of those, 14 received the vancomycin taper (two withdrew early) and 16 received the shorter vancomycin treatment and a fecal transplant. Participants reported their symptoms and experiences by telephone and sent in stool samples for testing if and when diarrhea occurred after treatment had begun. The study subjects also provided stool samples at baseline, one week into treatment, and at the 120-day mark. The doctors ended the trial after the first 30 patients completed their testing because, “There was only a 3.4% probability of finding a significant benefit for fecal transplants.”
The group noted that their study only included a single fecal transplant, whereas studies reporting higher success rates often included multiple transplants in order to achieve success. “Enema route was chosen for delivery as it was supported by data, practical, inexpensive, and well-accepted by patients,” they said. They also noted that fecal transplants can be administered by colonoscopy or nasojejunal tube. “Interestingly, the patients tolerated the volume of enema (about two cups) surprisingly well,” said Dr. Hota, adding, “We chose a higher volume to cover as much bowel surface area as possible while understanding that retention might be adversely affected.” She noted that some earlier literature on fecal transplants used up to 1.5L as their target, and that “no one truly knows how much FMT (in terms of donor stool amount and final FMT volume) is necessary to bring about positive results.”
The study results may also have been limited by the pre-treatment of patients with a two-week regimen of oral vancomycin. “This may have negatively impacted the intestinal microbiota such that a single fecal transplant was not sufficient for flora reconstitution,” the group speculated. In addition, the small number of patients in the study and their inability to conduct the study blindly also presented a limitation. “There are many unanswered questions that remain about FMT because there are so many variables that affect its effectiveness,” Dr. Hota said.
Although the team found the results to be “initially disappointing, as they may be for some others reading the results that a single FMT by enema appeared no better than oral vancomycin taper for resolving recurrent CDI,” Dr. Hota said, she emphasized that FMT is “an important treatment that can be very effective for patients with recurrent CDI.” She noted the need for “more comparative research on FMT methodologies,” and reported that a new program at the University of Toronto, the Microbiota Therapeutics Outcomes Program (MTOP), has this research as its focus. “In the meantime,” she concluded, “clinicians need to ensure that patients know that FMT will not cure recurrent CDI in all instances.”