Paul Feuerstadt, MD, FACG, AGAF: The question of refractory versus recurrent C difficile [Clostridioides difficile] is controversial. Recurrent C difficile is typically defined by patients who have classic C difficile diagnosed with stool assay, treated, and will recur in a fixed period with similar symptoms to when they presented originally. The issue arises with the timing for recurrence; some studies use 4 weeks, some studies use 8 weeks, some studies use 12 weeks, other studies use 24 weeks. The Centers for Disease Control and Prevention have landed on an 8-week follow-up, and most prospective randomized controlled trials use that 8-week marker.
Recurrent disease is fairly codified; however, refractory disease is not. Refractory disease is any patient who doesn’t seem to be responding to therapy but might not necessarily have that classic feeling better on antimicrobials and standard of care therapy, and then getting the symptoms again in the future.
A nice abstract was put forward at ID [Infectious Diseases] Week in October of 2020. Within that abstract they looked at the University of Virginia Health System for individuals who received fecal microbiota transplant for either recurrent infection or refractory infection. Within that abstract, they didn’t give clear definitions for recurrent and refractory infection, but what they put forward was that in the recurrent group, 5 out of 6 patients responded to a fecal transplant. Overall efficacy was 83%, whereas in the refractory group, 4 out of 7 patients responded, tabulating to about 57%.
What do we derive from this? What they derived from this is in a recurrent group of inpatients with C difficile, fecal transplants seem to work, and those numbers are on par with other studies. In the refractory group, they said you can give a fecal transplant, and it might work about 57% of the time. One of the most important pearls of understanding patients with C difficile and our treatments of C difficile is understanding that if a patient is not responding to vancomycin or fidaxomicin, they probably don’t have C difficile infection. Some 99.5% of the time, patients should have some response, at least halving the frequently of their bowels, and their stools should become somewhat formed.
One of the reasons I’ve enjoyed treating patients with C difficile, beyond curing them, is that a lot of individuals come to my office saying, “I have refractory C difficile.” And I sit down in the office with them and I say, “Well, what have you been treated with so far?” And they’ll tell me, “Well, I’ve received vancomycin.” And I’ll say, “Well, how many bowel movements were you having a day with the C difficile before the vancomycin?” And they say, “7 or 8.” And I’d say, “Well, once you received the vancomycin, how many bowel movements were you having?” And they’d say, “7 to 8.” And I’d say, “Well, you probably don’t have C difficile. It’s my responsibility to try to figure out what that is, what your diagnosis is, and how we can get you better.”
What can be a diagnosis that we see in patients with C difficile in the past? Post-infection irritable bowel syndrome [IBS] is common. It’s estimated that about 25% of patients who get C difficile will end up with post-infection IBS. How do we differentiate them? With a history similar to what I provided recently; we ask the patient about the frequency of their bowel habits. Typically, with a post-infection IBS, patients’ bowel habits will be about half or less of what they presented with initially with C difficile. You can ask the patients about the odor of their stool. Believe it or not, patients will say, “Oh no, it smells like C difficile right now,” or, “No, it smells like my previous odor.” If it smells like C difficile, most likely it’s C difficile. If it doesn’t, most likely not. And of course, the definition of irritable bowel syndrome; what is the definition of irritable bowel syndrome? An association of abdominal discomfort with bowel movements, either a relief or worsening of that discomfort.
As a gastroenterologist, I have the ability to also do a flexible sigmoidoscopy or a colonoscopy if the diagnoses is in question. Take some biopsies, we can look for a diagnosis like microscopic colitis. Of course, it’s also important to review the patient’s medication lists. A lot of these patients have multiple medical comorbidities. Perhaps they had a medication that was added recently that caused loose stools and softening of the stools, increased frequency. As a clinician, when it comes to recurrent C difficile, and when it comes to this “refractory C difficile,” unfortunately, we have to put on our thinking caps, go through a differential diagnosis and figure out what’s going on, to help those patients feel better.Sometimes it’s a simple recurrence, we can tease that out through history; sometimes it’s not, and we can tease that out through some of the tools we have available to us. But a clinical history is essential in differentiating those who have a true recurrence versus those who have a “refractory disease” that might be a result of another diagnosis.
Transcript Edited for Clarity