Emerging Treatment Options for C. Difficile Infections


Peter L. Salgo, MD: What are the barriers, if any, to FMT [fecal microbiota transplantation] for the treatment of recurrent CDI [Clostridioides difficile infection]?

Dale N. Gerding, MD: That’s unfortunately an important point. The FDA [Food and Drug Administration], in the past 2 years, has issued 3 warnings and cautions about the use of FMT. The first 1, a result of transmission of multidrug resistant organisms to susceptible patients, unfortunately had some fatal outcomes in those patients because they were highly immunosuppressed. That was followed by additional reports of transmission of toxigenic E. coli [Escherichia coli], which also resulted in some fatal outcomes following FMT. Then most recently, because of the presence of COVID-19 in the stool, there has been a caution from the FDA about using stool that has been acquired from donors during this COVID epidemic as a caution to primarily prevent transmission of the coronavirus with fecal transplant. These have been unfortunate occurrences, and we’re improving the screening of the donors. Each time something like this happens, additional screening tests are added for the donors. It is benefitting the entire process of FMT by getting better donor control in terms of management. The other factor that we still don’t know about is whether there will be long-term changes in underlying illness in patients who have their microbiome changed. It will probably take 5 to 10 years before we can answer questions like that.

Peter L. Salgo, MD: That brings to mind a question: Is there a difference in a response to fecal microbiota transplantation in refractory CDI versus recurrent CDI?

Dale N. Gerding, MD: Again, the bulk of experiments with FMT have been for recurrent CDI. We have had relatively few studies of recalcitrant disease or refractory disease, and the ones that have been done have been largely done by administering FMT through colonoscopy. An investigator in Italy, Giovanni] Cammarota Agostino Gemelli of the IRCCS University Hospital Foundation, had done some early studies. By doing colonoscopy, you can tell if a patient has a pseudomembrane or not. About half of the patients, based on our early studies, will have pseudomembranes present if they have C diff diarrhea. What Cammarota found was that he needed to do multiple fecal transplants in these patients and try to resolve the pseudomembranes. He did it in an unusual way. He administered vancomycin while he gave fecal transplants. I’ve never quite understood how you can have both vancomycin being administered, which should be detrimental to your microbiota, and at the same time be administering fecal transplant. It’s always been a mystery, but it’s been much more difficult to treat refractory C diff infection than it is to treat prevention of recurrence.

Peter L. Salgo, MD: Are there any common threads, key factors associated with the negative outcomes from fecal transplants?

Dale N. Gerding, MD: Yeah. There are very few failures as everyone has pointed out. Generally, in comparator trials, the rates of response are up in the 80% to 90% range. One recent publication has shown that non-responders are probably people who have irritable bowel syndrome, and that they probably entered these trials inappropriately and have persistent diarrhea after a failure of the FMT. The other interesting finding about this study was that the responders seemed to do better if they’d had a long course of antibiotic therapy preceding FMT. That’s been found by other investigators as well. A long course of vancomycin or a long vancomycin taper and pulse course followed by FMT generally gives you the highest response rates.

Peter L. Salgo, MD: If you enjoyed this content, you should subscribe. We have an e-newsletter, and you can receive upcoming Peer Exchanges and other great content in your inbox—that’s right, electronically. I’ll see you next time. I’m Dr Peter Salgo. Thanks again for watching.

Transcript Edited for Clarity

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