Colleen Kelly, MD RES ’06, clinical assistant professor of medicine and a gastroenterologist at the Women’s Medicine Collaborative in Providence, is a leading expert in fecal microbiota transplants (FMT) to treat recurrent Clostridium difficile infection, which infects as many as 3 million patients each year in the US—and kills about 50,000 of them. These infections are caused by antibiotics and are becoming more resistant to routine therapy.
Kelly has treated more than 140 patients with FMT and is the principal investigator for an NIH-funded randomized controlled clinical trial for the treatment of relapsing C. difficile infection. FMT involves transferring the “good” microorganisms from a healthy donor into a patient with C. diff infection. These bacteria then begin to grow in the patient’s colon and prevent C. diff from overgrowing again. Published data suggest the therapy is up to 94 percent effective.
Why is toxigenic C. difficile dangerous? How do antibiotics cause this?
How did your research begin?
C. difficile infection can range from mild diarrhea to severe. At its worst, C. diff can present with severe systemic toxicity including shock, multisystem organ failure, lactic acidosis, and even result in death. Antibiotics cause damage to the “good bacteria”—the healthy communities of anaerobes that are normally dominant in a healthy colon. These anaerobes normally limit the growth and expansion of C. diff. When they are wiped out by antibiotics, C. diff can proliferate, produce toxin, and result in disease.
I started doing fecal transplants because I had a patient with recurrent C. difficile who was not getting better after six months of standard therapies. It seemed logical and safe, and it was her only option. When it worked, I was referred a few more patients from Boston, where they were not yet doing fecal transplants. It was effective in every one of them. After about a year, I wondered why everybody wasn’t doing it. That led me to designing a study, applying for funding through NIH, and securing an IND [Investigational New Drug] status from the FDA. The FDA considers fecal transplant a “drug” and a “biologic” and requires an application, just as they would from a pharmaceutical company seeking to test a new drug. I started a randomized double-blind clinical trial in 2012 and we should be completing enrollment sometime this summer.
Were you nervous when you treated your first patient and implanted screened stool from a healthy donor into her via a colonoscope?
Very. I wasn’t sure exactly how to do it, whether it would work, whether I could cause an infection. I read everything I could find, talked to doctors who had done it, and became more convinced about the safety. In more than 50 years of fecal transplants, there haven’t been any reports of infections transmitted. With the first patient I was just worried it wouldn’t work. I didn’t know what else I could do for her.