The incidence of Clostridium difficile infection (CDI) has risen sharply over the last two decades. The number of cases among hospitalized adults tripled between 1993 and 2005 and more than doubled between 2001 and 2005. Mortality rates have also increased, coincident with the emergence of the hypervirulent NAP1/BI/027 strain.

Multiple relapses are increasingly common, too, with 20 to 30 percent of patients experiencing at least one recurrence two to four weeks after completing vancomycin therapy. Some patients who undergo emergency colectomy continue to experience symptoms post-surgery. Although half of all CDI cases occur in people under age 65, older adults are far more likely to have severe disease with associated complications and multiple relapses.

"Clostridium difficile is a huge problem for the elderly," says Robert Orenstein, D.O., of Mayo Clinic in Arizona. "There is a large population of older patients with an ongoing cycle of relapse for which there are few conventional options."

But, he says, one therapy — fecal microbiota transplantation (FMT or fecal transplantation) — has proved highly effective at eradicating C. difficile infection and restoring a healthy gut microbiota.

"Patients with CDI are missing certain gut flora, usually as a result of antibiotic use," Dr. Orenstein explains. "I suspect some kind of signaling takes place between healthy bacteria and the mucosa of the gut, and without that signaling, C. difficile can take over. Restoring the missing flora seems to be the key."

The Mayo Clinic in Arizona FMT team first performed a colonoscopic fecal transplant in 2011 for a patient with severe refractory C. difficile pseudomembranous colitis, using donated stool from the patient's brother.

"Unbelievably, the patient left the hospital 24 hours after the procedure, after having been bedridden for weeks," Dr. Orenstein says. "That opened my eyes to the possibilities for helping others."

Since then, Mayo Clinic in Arizona has performed 24 fecal microbiota transplants for CDI patients. In every case, the infection was completely eradicated — often within hours or days — although two patients with comorbidities experienced relapses. Cheryl L. Griesbach, R.N., who was instrumental in developing Mayo's fecal transplant program, says the positive results have been overwhelming. "I've talked to every patient. After having been desperately ill and homebound, the dramatic change in their quality of life is truly phenomenal," she says.

Dr. Orenstein points out that Mayo's program is distinguished by a rigorous protocol for evaluating recipients and donors. "Our focus is on safety, measuring outcomes, appropriate follow-up and ongoing process improvement," he says. "Without regulation or standards, if something goes wrong, that could mean the end of this procedure for people who really need it."

How Mayo's program works

Fecal transplantation can be performed via nasogastric tube, nasojejunal tube, upper tract endoscopy, colonoscopy and retention enema. Dr. Orenstein says he prefers colonoscopic infusion because it safely and effectively delivers healthy bacteria to the site of most C. difficile infections.

"If something goes wrong with nasogastric insertion, the complications could be disastrous," he notes. "And implanting stool in the small bowel might lead to bacterial overgrowth. We don't know, but that would be one of my concerns. From our experience, the terminal ileum is the optimal site."

Mayo currently uses fecal transplantation only for patients with relapsing CDI. Exclusion criteria include concurrent gastrointestinal illnesses and the inability to undergo colonoscopy. Immunosuppressed and transplant patients — with the exception of recent bone marrow transplants — may qualify.

Griesbach says, "The beauty of the procedure is that even when patients have an ongoing disease process, their quality of life is tremendously improved after the transplant. To see such turnarounds in a relatively short amount of time is miraculous. It's similar to what we saw with HIV-protease inhibitors."

Concerns about the safety of banked stool and patient preference have so far limited donors to family members, but a future project will involve collecting and banking donor stool for study and transplants. Another project for which Dr. Orenstein is now recruiting patients will study fecal transplantation in the management of multi-drug resistant pathogens, particularly vancomycin-resistant enterococci (VRE).

The sky is the limit

Fecal transplantation has generated "a lot of buzz for lots of illnesses," Dr. Orenstein says, and both he and Griesbach feel the procedure's potential has barely been tapped.

"Its use in C. difficile has been well established, but much of the rest is mainly anecdotal," he says. "There is some baseline evidence that it might be effective for IBS, but that hasn't been looked at in a controlled manner. Some physicians claim to have great success treating ulcerative colitis and celiac disease. And it's been looked at for obesity, diabetes and rheumatoid arthritis because some of the signals for the gut are pro-inflammatory for RA. But it's difficult to get real data."

He adds, "There is a lot of potential on the research side, and we can put research into practice pretty quickly. We have built a clinical infrastructure and we are building the research infrastructure. Once we see what works, we can provide that service to patients."

Noting that FMT shows some potential for treating Parkinson's disease, Griesbach says she is excited about future interest in the procedure within the institution. "It is crucial to start getting data so these projects can move forward. It's only limited by our desire, imagination and cost," she says.

"The microbiome of the gut is not inactive; it's diverse and plays many roles in health and well-being that are just now being explored," Dr. Orenstein points out. "With molecular biology and the sequencing of these species, this can only get bigger. It's like the beginning of the space program."

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