American Journal of Gastroenterology Lecture

Intestinal Microbiota and the Role of Fecal Microbiota Transplant (FMT) in Treatment of C. difficile Infection

Lawrence J Brandt MD; MACG

Disclosures

Am J Gastroenterol. 2013;108(2):177-185. 

In This Article

CDI and FMT: Long-term Follow-up and Safety Issues

In the only long-term follow-up of FMT to date, a five-medical center cross-country joint effort, 77 patients who had had FMT and were followed for more than 3 months experienced a 91% primary cure rate and a 98% secondary cure rate, the latter defined as cure enabled by use of antibiotics to which the patient hadn't responded to before the FMT or by a second FMT.[37] It is interesting that 97% of these patients stated they would have another FMT were they to develop CDI again and 58% said they would choose to have FMT rather than antibiotics. It is not unusual for patients to develop some gastrointestinal complaints or altered bowel habit for several days after FMT, including absence of bowel movement, abdominal cramping, gurgling bowel sounds, or increased feelings of gaseousness. Of the 77 subjects in this study, four developed an autoimmune disease (rheumatoid arthritis, Sjogren syndrome, idiopathic thrombocytopenic purpura, and peripheral neuropathy) at some time after the FMT, although a clear relationship between the new disease and FMT was not evident. Safety of FMT in immunosuppressed patients needs to be established, although limited experience to date would suggest immune-compromise is not of concern. I personally have performed FMT in many patients who were either on glucocorticoids, immunosuppressive (6-mercaptopurine, azathioprine), or biological agents (infliximab, adalimumab), or who had diseases or therapies characterized by immunocompromise (kidney transplant, chronic lymphocytic leukemia, lymphoma, primary immune deficiency, Schwachman–Diamond syndrome) without ill effect. Nonetheless, safety remains the prime consideration and larger numbers of observations in controlled circumstances are needed. Controlled trials also are necessary to prove the efficacy of FMT, and to determine the optimal route of administration among other variables. Two such randomized, controlled trials are pending; one that compares conventional vancomycin therapy alone and with bowel lavage, or with bowel lavage plus FMT is currently in progress.[38] A recently approved NIH-funded study, principal investigators of which are Dr Colleen Kelly and I, will evaluate FMT in 80 patients with at least three bouts of CDI, and compare results of blinded FMT, using either donor or recipient stool for the transplant.

The use of stool for such transplants is but the first step in a long journey. Stool is the ultimate probiotic but greater knowledge of the intestinal microbiota and its functions will certainly enable us to administer one or more intestinal micro-organisms or genetically refined products derived from stool rather than stool itself to treat CDI. The next step in this journey has already been taken with the development of a standardized filtered, frozen preparation of stool for FMT and use of a "universal donor".[36]

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