March 28, 2015
The incidence of Clostridium difficile infection (CDI) has risen sharply over the last two decades, with 500,000 cases reported in the United States in 2010 alone. Multiple relapses are also increasingly common, with up to 25 percent of patients experiencing at least one recurrence of disease two to four weeks after completing standard antibiotic therapy. Recurrence rates rise with each subsequent episode, and as many as 40 percent of patients are likely to relapse after the second episode and 65 percent or more after a third episode.
Clostridium difficile infection (CDI)
CDI mainly results from antibiotic-induced dysbiosis.
CDI can occur without antibiotic exposure, but it mainly results from antibiotic-induced dysbiosis — disruption of the microbial composition of the gut and its ability to resist colonization by C. difficile. Traditional therapy for relapsing CDI — usually oral metronidazole and vancomycin — has limited success because it fails to correct a disordered microbiome and may contribute to further dysbiosis.
Fecal microbiota transplantation (FMT), on the other hand, which is increasingly recognized as a safe and effective intervention for patients with recurrent CDI, restores microbial homeostasis and has proved far superior to vancomycin. It is not yet a first line therapy, however, and is typically only considered in patients who have had three or more documented cases of CDI or two CDI-related hospitalizations and failed a long vancomycin taper.
FMT for recurrent CDI is available at all Mayo Clinic sites, where a variety of C. difficile and microbiome studies also are underway.
FMT at Mayo Clinic's campus in Florida
Maria I. Vazquez Roque, M.D., a gastroenterologist at Mayo Clinic's campus in Jacksonville, Florida, observes that the Food and Drug Administration (FDA) initially proposed requiring investigational new drug (IND) status for FMT procedures. That stance would have denied access to the procedure for many, if not most, patients and was later changed. For the time being, the FDA exercises enforced discretion.
"The IND would have been too cumbersome and expensive, but once that changed, we were able to start performing the procedure," she says. "We have completed nine FMTs since January 2014, with a 100 percent success rate and no recurrences. We have a nurse who contacts patients at one week and at one, three and six months, so we have good data about relapses.
"In terms of recovery, what we see is that within one or two days, people are starting to feel better. Patients who are on suppressive doses of vancomycin are able to discontinue it. It's thrilling what a difference FMT makes. For some, there is an initial yuck factor, but in my experience, once it's known how much this is helping patients and how appreciative they are, that goes away."
FMT at Mayo Clinic's campus in Arizona
Since 2011, approximately 125 FMTs have been performed at Mayo Clinic's campus in Phoenix, with an approximate 90 percent success rate. A retrospective analysis of Arizona's initial experience, which appeared in the August 2013 issue of Mayo Clinic Proceedings, found the procedure safe, highly effective and relatively simple to implement.
"Overall, we remain very impressed with the usefulness of FMT in treating multiple recurrences and refractory cases of C. difficile infection and continue to receive many referrals, both locally and from around the country," says John K. DiBaise, M.D., a gastroenterologist at Mayo's Arizona campus. "We aren't using frozen specimens but have gone to using standard donors, which has reduced patient costs and the efficiency of getting the procedure completed. Another thing that sets our program apart is the team approach, which includes members from infectious diseases, gastroenterology and endoscopy, with a nurse coordinator facilitating all aspects of the procedure."
Researchers in Arizona and at Mayo Clinic's campus in Rochester, Minnesota, are retrospectively evaluating the effect of FMT on CDI patients with concomitant inflammatory bowel disease (IBD) and prospectively analyzing recipient quality of life and satisfaction with the procedure. Other studies are in the preliminary stages, including an investigation into the use of FMT to decolonize vancomycin-resistant enterococcus in the gut and planning studies to evaluate FMT in the setting of IBD, irritable bowel syndrome and other conditions.
FMT at Mayo Clinic's campus in Minnesota
Physicians at Mayo Clinic's campus in Rochester, Minnesota, have performed about 180 FMTs — mainly using specimens from standard volunteer donors — with an overall 90 percent success rate. Frozen stored donor samples are now also being used to make scheduling FMT more convenient and decrease uncertainty of donor availability. The campus has a dedicated CDI clinic serving patients with first-time infections as well as recurring and complicated CDI.
"The clinic is staffed by experienced physicians and a team of study coordinators, nurses, lab technicians and microbiome researchers who have a special interest in C. difficile," says Sahil Khanna, MBBS, who co-directs the clinic. "In addition to managing patients with CDI, we are doing research on engraftment of gut bacteria within the colon after FMT and are part of clinical trials to evaluate newer modalities for FMT, including enema and capsule-based forms."
For more information
Patel NC, et al. Fecal microbiota transplant for recurrent Clostridium difficile infection: Mayo Clinic in Arizona experience. Mayo Clinic Proceedings. 2013;88:799.