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Pills to Treat Recurring C Diff?

By Jamie Santa Cruz

Delivering fecal microbiota to the colon via oral capsules may provide a safe and effective treatment for patients who suffer multiple recurrences of C diff.

For patients who experience multiple Clostridium difficile (C diff)recurrences, among the most effective treatments currently available is transplanting fecal microbiota from a healthy donor into the patient’s gut. Research suggests that nine of 10 such transplants successfully prevent a recurrence of the infection,1,2 which is linked to about 14,000 deaths each year, according to the Centers for Disease Control and Prevention. But such treatments are not widely available, and patients sometimes travel significant distances to find a clinician who performs the procedure.

However, Thomas Louie, MD, a professor of infectious diseases and microbiology at the University of Calgary in Alberta, Canada, is pioneering a new method of combating C diff that may soon make similar treatment more widely accessible: fecal microbiota capsules.

Typically, fecal microbiota transplants are delivered via colonoscopy, a nasal-gastric tube, or enema. Although the concept of fecal microbiota transplants via gelatin capsules has been proposed previously, says Cliff McDonald, MD, chief of the prevention and response branch of the division of healthcare quality promotion at the Centers for Disease Control and Prevention, Louie appears to be the only one who has moved the idea beyond the concept stage and actually offered the capsules to patients.

Louie’s method is to take fresh stool from a donor, usually a patient’s relative, and then process it until the stool is reduced to bacteria. After processing, the mixture is packaged in three layers of gelatin capsules to ensure that the bacteria are delivered to the small intestine rather than dissolving in the stomach. His results to date are promising: Of the 27 patients who participated in an initial trial of the pills, none had a recurrence of C diff following the treatment, though all had experienced at least four bouts of the infection previously.3

Pills’ Advantages and Disadvantages
Louie’s treatment essentially is the same as existing treatments being given through alternate means, according to Colleen Kraft, MD, an assistant professor of infectious diseases at Emory University Hospital in Atlanta. “It’s just packaged differently,” she says.

Although the treatment may be the same, the capsule packaging avoids several risks associated with alternative methods: It doesn’t require anesthesia as does a colonoscopy, and there are no worries about aspiration from feeding tubes.

At the same time, since the pills pass from the mouth downward through the digestive system, the fecal microbiota are guaranteed to reach through the whole colon, which sometimes is difficult to ensure with an enema.

The capsules’ key limitation is that an individual capsule can hold only a relatively small amount of intestinal bacteria, which means patients must swallow a significant quantity of the pills. In the treatments Louie has done so far, patients have ingested a total of two to three dozen capsules.

According to McDonald, the sheer number of pills required could be a significant turnoff to some potential patients. “How many capsules can someone reasonably take?” he asks. “These are pretty big capsules [Louie] is using, and that’s part of the problem: Some people really have trouble swallowing these big capsules.” For that reason, he believes alternate methods of delivery may still be preferable for some patients.

Hurdles to Overcome
In 2013, the FDA announced new regulations requiring that an investigational new drug application be submitted prior to any fecal microbiota transplant, which temporarily brought most transplants in the United States to a halt. But under pressure from physicians who stressed the unique effectiveness of microbiota transplants for combatting C diff, the FDA later announced that it would exercise enforcemen discretion in cases involving multiple recurrences of the infection.

The announcement offered what McDonald calls a sort of green light for physicians to go ahead with trantsplants in cases of multiple recurrence, and his sense is that the transplants have been growing in popularity since the FDA relaxed its regulatory oversight.

Interest in the procedure suggests a significant market for the pills if they become widely available, but before that can happen, several obstacles remain to be overcome. For instance, the pills have been tested only in small trials. “All of these things always need to be larger scale,” Kraft says. “There needs to be a randomized control trial.” Such a trial will help to sort out a variety of questions that currently exist about the method, such as its efficacy in a larger population, the proper dosage, and what happens if a pill breaks in a patient’s mouth.

Beyond trials, changing public perception of the pills—and of fecal transplants in general—also will be key, as the idea of swallowing capsules of human stool turns off many people. “We’ve really got to change [the terminology] and not talk about stool or feces,” McDonald says.

The FDA continues to use the term “fecal microbiota transplants,” but the preferable term, in McDonald’s view, is “intestinal microbiota.” Not only is that term less repulsive for patients, but it also is more accurate. “There is some processing being done. This is not just fresh feces,” he notes.

Greater commercialization of the process also may be necessary before the capsules can grow in popularity. Currently, Louie makes all of his pills individually for each patient, which means it’s a logistical challenge to offer the pills on a larger scale. “Having a commercial entity coming in and saying, ‘Here’s a whole step-by-step process or kit that helps you process stool into intestinal microbiota capsules’—I think something like that stepping in would make a difference,” McDonald says.

One possibility for the future development and commercialization of the pills is moving away from human stool altogether. At present, it’s still not clear which particular bacteria and microorganisms in the stool are the effective components, but Colleen Kelly, MD, a clinical assistant professor of medicine at Brown University’s Warren Alpert Medical School, anticipates that further research will eventually isolate those bacteria.

After that point, the bacteria could be cultured in a laboratory and then placed in pills, bypassing human donors altogether. “I think that’s really where this is ultimately going to go,” says Kelly, who currently performs four to six fecal microbiota transplants per month via either colonoscopy or sigmoidoscopy in her own practice. But she notes that such a product won’t be available in the immediate future

Future Potential
The capsules’ potential benefits make the prospect of commercialized pills exciting. At present, Kelly’s own practice is hampered by the fact that current methods of transplantation are labor intensive, since each transplant requires finding and screening an individual donor. “I’ve been doing these for five years as a major focus of my practice, and I’ve only just this morning treated my 131st patient. So I’m working like crazy, and there are only so many of these I can do,” she says.

It’s a problem that she hopes the pills will resolve shortly. “If you can avoid instrumenting people, which adds expense and risk, and you can develop something that’s as effective in pill form, then I think it’s going to make this treatment … available to many, many more patients,” she says.

Kraft likewise is optimistic. Though it likely will be some time before current transplantation methods become obsolete, she envisions the capsule packaging as the future of the field. In fact, she goes so far as to say that she eventually would like to offer the pills to every patient who has had a course of antibiotics, not just to those suffering from C diff.

“As with everything else, we just need to continue to vet the process,” she says. “But I think [pills] will and should replace the traditional fecal transplant method.”

— Jamie Santa Cruz is a freelance writer based in New York City.


1. Burke KE, Lamont JT. Fecal transplantation for recurrent Clostridium difficile infection in older adults: a review. J Am Geriatr Soc. 2013;61(8):1394-1398.

2. Kelly CR, de Leon L, Jasutkar N. Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. J Clin Gastroenterol. 2012;46(2):145-149.

3. Fecal transplant pill knocks out recurrent C. diff infection, study shows. IDWeek website. http://idweek.org/pr-2013-cdiff/. Accessed November 7, 2013.