ecal transplants are increasingly becoming a mainstream treatment.
For the first time, an influential medical group is recommending the procedure — in which donor fecal matter is transferred to a patient — for individuals who have repeatedly failed standard treatments for severe diarrhea caused by Clostridium difficile, commonly known as C. diff.
The Infectious Diseases Society of America issued the new guidelines Thursday for combatting the bacterial infection, which sickens nearly half a million Americans every year.
“We are now including the recommendation … that they be at least considered for fecal microbiome transplantation,” said Dr. Clifford McDonald, one of the authors of the new IDSA guidelines. He is the associate director for science in the Division of Healthcare Quality Promotion at the Centers for Disease Control and Prevention.
C. diff is an opportunistic pathogen, invading the gut after antibiotics have wiped out the healthy bacteria that populate the gastrointestinal tract. The illness is most dangerous for people who are older than 65 or whose immune systems are weak. An estimated 15,000 to 30,000 Americans die from it each year, and treatment costs run to more than $4.8 billion.
Standard treatment is yet another antibiotic, but the IDSA has changed its guidance on which drug to use and how. It urges “antibiotic stewardship” to reduce resistance to the drugs that fight infections yet in some people destroy healthy microbes, too. The society also encourages “diagnostic stewardship” — testing the right people so carriers for whom the bacterium is harmless aren’t needlessly given antibiotics just because they have diarrhea.
C. diff releases spores that people can easily spread to one another. Healthy people develop antibodies to the toxin released by the bacteria so they don’t get sick, but they can be colonized by C. diff without being infected.
“If you change a diaper, you probably get spores in your mouth but you don’t get C. diff infection. Health care workers do not appear to have C. diff infection, yet they are around it all the time,” said McDonald.
The ones who are vulnerable are patients taking antibiotics for another illness, leaving them without healthy gut microbes. When they first contract a C. diff infection, the recommended treatment they receive would now be a course of oral vancomycin or fidaxomicin, a departure from previously recommended — and less expensive — metronidazole, which recent studies have shown to be less effective.
C. diff is so insidious because the chances of it coming back again and again get higher and higher. The risk of having a repeat infection is 20 percent to 30 percent after the first bout, rising to 40 percent after a second, and 60 percent after a third. The misery of severe diarrhea can disrupt people’s lives, whether they live at home or in nursing homes. One study cited by the IDSA found that C. diff infections outnumber MRSA infections, a type of antibiotic-resistant staph infection, in long-term care facilities.
Patients with so many recurrences are the ones IDSA considers candidates for fecal transplantation. The American College of Gastroenterology took a similar stance in recommending fecal transplants for some patients with C. diff in 2013.
Alternatives are continued antibiotics or, in severe cases, surgery to remove their damaged colons.
The idea behind fecal transplants is akin to other forms of transplantation: take something from a healthy person to replace what the patient has lost, in this case a healthy microbiome. Donor stool can be delivered by colonoscopy, sigmoidoscopy, or in the form of capsules. A recent study published in the Journal of the American Medical Association compared the two routes and found both worked about as well.
Stool donors face stricter scrutiny than blood donors, said Dr. Elizabeth Hohmann, an infectious diseases physician at Massachusetts General Hospital, who has done fecal microbiota transplantation, or FMT, in more than 300 patients. She offers the oral capsules exclusively, which are made in her lab in a program that is under the supervision of the Food and Drug Administration.
Donors must have no history of medical problems, be taking no medications, have normal body weight, and undergo lab testing for infectious diseases including HIV, hepatitis, syphilis, or any intestinal pathogen. “They’re really screamingly healthy people,” said Hohmann, whose research has been supported by Seres Therapeutics, a company that develops microbiome therapeutics.
The success rates for fecal transplants approach 90 percent, IDSA notes.
The FDA considers FMT an “investigational new drug,” but has issued guidance saying it will “exercise discretionary enforcement” when it is used for people with multiple recurrences of C. diff infection. That means fecal transplants are not subject to the same standardization that a drug might be, such as dose or formulation.
Although a growing body of evidence has concluded that the procedure is safe and effective, long-term data are yet to come. The American Gastroenterological Association is recruiting patients for a new registry, funded by the National Institute of Allergy and Infectious Diseases, to follow 4,000 patients and their outcomes for 10 years.
One concern about fecal transplants is that a transplanted microbiome could transplant more than a healthy gut. Case reports suggest weight gain might be transferred, too. The microbiome has also been linked to depression, diabetes, allergy and asthma.
Dr. Colleen Kelly, an associate professor of medicine at Brown University’s Warren Alpert School of Medicine, said she’s been waiting eagerly for new guidelines. She performed her first fecal transplant in 2008 and in most cases acquires stool from a nonprofit stool bank, OpenBiome.
“We really know it’s the most effective treatment for multiply recurrent C. diff when patients have failed all the standard antibiotic therapy,” she said. “I’m happy they agreed and put it in the guidelines. They understand patients don’t have a lot of options.”