A yucky treatment that works for C. diff

A simple and effective procedure for a life-threatening illness has become more difficult to obtain.

The illness is clostridium difficile, or C. diff for short. It’s a debilitating intestinal disease in which the C. diff bacterium takes over a person’s intestinal tract when good bacteria are killed off. The results are extreme diarrhea, dehydration, cramping, weight loss and nausea, among other symptoms. C. diff cases in the U.S. are believed to be about 500,000 per year, with between 14,000 and 30,000 deaths, compared to 15,529 annual AIDS-related deaths in the U.S. in 2010.

Its main causes are use of wide-spectrum antibiotics that kill the good bacteria and community contamination, particularly in hospitals and nursing homes.

The procedure is one that’s basic, but not that pleasant to contemplate: fecal microbiota transplant.

Fecal transplants have been used for years in Europe and Australia, but only recently in the U.S., to treat hard-to-cure intestinal ailments, mainly C. diff. There was no regulation of the procedure in the U.S. until 2013. That’s when the Food and Drug Administration classified fecal donations as an unapproved drug that could only be used in approved trial situations.

It modified that decision later in the year, but the regulation still has made fecal transplants less available than before and led to some confusion in the process.

The procedure is yucky to consider but has a 90 percent success rate for C. diff victims: A physician secures feces from a healthy donor, screens it for disease, combines it with a saline solution, and infuses it into the patient’s intestines through a colonoscopy. Good bacteria from the donated stool repopulates the patient’s intestinal tract so that the C. diff bacterium is shut down.

And although it’s unpleasant to think about, it also works—well. But, even before the FDA slowed down its use, it was infrequently performed in the U.S. due to lack of knowledge about the procedure or an aversion to it.

That frustrates proponents of the procedure like Catherine Duff, founder of the Fecal Transplant Foundation. Herself a C. diff survivor after being diagnosed eight times with the infection between 2005 and 2012, Duff says the procedure needs to be encouraged, not inhibited. About 150,000 victims of C. diff in the U.S. could benefit from fecal transplants, Duff estimates.

The FDA did somewhat reverse itself following a May 2013 workshop on its more restrictive guidelines. Duff, the only C. diff survivor to speak at the conference, has been credited with having the most influence on the guidelines change.

“Basically I just told how fecal transplant had saved my life, and that there were hundreds of thousands of people out there” who needed the procedure, Duff says.

Duff’s cases were linked to antibiotic use or exposure to the C. diff bacterium in a hospital setting.

It was after treatment with antibiotics had failed her again that Duff turned to fecal transplant. Unable to find a physician to perform the procedure in 2012, she and her husband managed a home version using an enema after her husband’s stool had been checked for disease. She came down with it again later that year, though, and finally one of her doctors agreed to perform a fecal transplant.

It worked, and she has been symptom-free since then.

Her experience led her to start the foundation, which provides resources for both patients and doctors while trying to improve communication about the practice and encourage further research.

That’s still a challenge, though, even in light of the FDA’s toned-down regulations.

At first, the FDA ruled that feces used in fecal transplants were a “new drug” and therefore had to pass drug trials, which can stretch on for years, before being used. Classification as an “investigational new drug” also threatened to discourage doctors from performing fecal transplants because of the expense and complications involved in setting up an IND trial program.

The agency issued new draft guidelines in July 2013 as a result of the May hearing. The basic rules, according to Rachael Conklin, consumer safety officer in the FDA, now are:

• Fecal transplant is being reserved for use on C. diff patients that are “not responsive to standard therapies,” such as antibiotics. It doesn’t appear that it can be used for other intestinal ailments.
• The donated stool has to be from “a donor that is known to either the patient or the treating licensed health care provider.”
• Both donor and stool have to be screened and tested.

Duff and other pro-transplant activists are glad the FDA eased up, but are still concerned that the rules are too restrictive or confusing.

For one thing, requiring donors to be “known by” the patient or physician rules out use of stool banks that were created before the FDA decided to regulate the process. The stool banks—there’s one at the Massachusetts Institute of Technology and one at Emory University—test and freeze the donations. The Fecal Transplant Foundation and the MIT bank, known as Open Biome, drafted letters objecting to this rule.

“This makes no sense because research has shown it’s no more efficacious to use a donor that’s ‘known by’ the donor or doctor or who’s a family member than it is to use a universal donor,” Duff says. “Research has also shown there’s no difference between fresh stool and frozen stool.”

There’s also the problem of what “known by” means. Does that mean, Duff notes, that if you or your doctor know them only through a social media network they qualify? Asked for clarification, the FDA’s Conklin replied:

“The donor cannot be an anonymous donor or someone that the physician or patient have no knowledge of prior to the donation. The FDA is not providing a strict interpretation of the exact way in which a donor needs to be known to the patient or physician.”

Duff continues her work while waiting for the FDA to issue final guidance. Her foundation’s website lists 75 doctors willing to perform fecal transplants, but it’s not enough, she says.

“Even if these 75 providers did fecal transplants 24 hours a day, seven days a week, they couldn’t meet the need,” she says. “We need more providers. We need more funds so we can develop educational materials to send out to doctors and to try to help doctors develop fecal transplant programs because there are so many people who don’t have someone close enough to them (to perform the procedure) that they’re dying because they can’t get a fecal transplant.”

She agrees that donated stool should be screened for disease. Having the feces of someone with hepatitis, HIV/AIDS, or other sexually transmitted diseases transplanted into a victim could otherwise be a problem. In addition, some donors could be asymptomatic C. diff carriers; their donated stool would simply reinfect the patient.

The foundation is also urging the FDA to loosen restrictions on the use of fecal transplant for other intestinal maladies like Crohn’s disease, irritable bowel syndrome, and colitis. The success rate of fecal transplants in these situations is in the 20-30 percent range—not as high as for C. diff, but not bad.

Meanwhile, research continues on isolating the microbiota found in healthy stool and administering it in capsule form so that colonoscopies can be avoided altogether.

“I hope the process of isolating the microbiota that is within fecal matter is perfected and that it becomes economically feasible,” Duff says.

But while she agrees with some of the FDA’s regulation efforts regarding fecal transplants, she also would like the agency to approach it not as a drug, but as a biologic. It would then be overseen like blood-like blood donations or transfusions, tissue donations, or organ donations.