Expert Perspectives on Advances in the Management of C. Difficile - Episode 5

C. Difficile: A Differential Diagnosis

January 8, 2021

Important things to understand about diagnosing C. difficile and recommendations for properly differentiating the condition from other diseases when working-up a patient.

Peter L. Salgo, MD: Let’s get a road map for our colleagues. What is the best way to approach a patient in terms of diagnosis when a patient presents with diarrhea? Teena, do you want to start with that?

Teena Chopra, MD, MPH: Sure. The first important thing is you want to realize that Clostridium difficile is a disease with a spectrum. It can be anywhere from mild to very severe sepsis, pseudomembranous colitis, fulminant colitis, and death. So you want to make the diagnosis correctly. The first important thing is using your clinical judgment. A strong clinical acumen when a patient has more than 3 diarrheal stools within 24 hours to make the diagnosis with this definition in combination with our diagnostic tests.

The diagnostic tests can vary. You can have various kinds of diagnostic tests that are out there, and our Infectious Diseases Society of America very nicely outlined how to use these diagnostic tests. There are nucleic acid amplification tests, and there are the toxin and the GDH [glutamate dehydrogenase] antigen test, whether they’re used in combination or alone.

Peter L. Salgo, MD: Let me stop you for just a minute. Do you just jump to these tests? There are people who get diarrhea from antibiotics who do not have C diff. They simply take an antibiotic and they have diarrhea. There are people who have irritable bowel syndrome and they present with diarrhea. Does everybody with diarrhea go right to the genetic tests and the other tests you’re outlining? Or do you step back?

Teena Chopra, MD, MPH: That’s a great point. As I said, you have to make the clinical diagnosis first. You cannot test every patient for C diff. In the right clinical setting…we talked about all the risk factors of C diff. If a patient meets those criteria—for example, an older patient who’s presenting with fever, has a white [blood cell] count and has more than 3 diarrheal stools in 24 hours, this kind of patient will fit into the picture of a diagnosis of C diff. But diarrhea, as you said, can be antibiotic associated or it can be because of other causes like parasites, traveler’s diarrhea, and things like that. You have to make that clinical diagnosis. We have C diff that can be toxigenic and nontoxigenic, and some patients who maybe just colonized, so you cannot get every patient for C diff.

Joseph Reilly, BS, PharmD, BCGP: If I could just add how important it is what Teena said, especially if you have the re-sensitive testing. What you don’t want to do is wind up having positive tests for patients who are colonized and really don’t have C diff infection. Now that we have pay-for-performance with hospitals and public reporting of our CDI [Clostridium difficile infection] rates, hospitals are motivated to make sure that their CDI rates are below the limit that it should be because there are significant financial losses associated with having higher CDI rates.

Peter Feuerstadt, MD, FACG, AGAF: Right. That’s really important. Teena and Joe pointed out essential elements. But we need to broaden the differential diagnosis and thinking about the patient and not just what tests, and not having a knee-jerk reaction, “Oh, diarrhea, need to check C diff.”

In a patient with inflammatory bowel disease [IBD], absolutely. It’s bordering on malpractice if you don’t check a C difficile stool assay. But the overall majority of the population that presents to clinician and caregivers doesn’t have inflammatory bowel disease. We need to take a step back and think about that clinical presentation: Is the diarrhea bloody? Is it nonbloody? Is it a secretory diarrhea? Is it an osmotic diarrhea?

All these factors that we generate our differential diagnoses around need to be considered. Irritable bowel syndrome is certainly a consideration. Also a consideration I’m sure we’ll discuss a little later is a post infection irritable bowel syndrome and how we tease that out, which can be very complicated. But speaking to Joe’s point relating to this, those patients that have had C difficile already, and they get another set of diarrhea, another change in bowel habit, thinking about them critically and whether this seems consistent with a recurrence of C diff or something else is essential that all of us direct therapy appropriately for those patients.

Peter L. Salgo, MD: It’s worth remembering that just because somebody has irritable bowel disease doesn’t mean they don’t have C diff. They can coexist, which complicates everything.

Peter Feuerstadt, MD, FACG, AGAF: Yes. It’s essential for any patient with inflammatory bowel disease who is presenting with an exacerbation of their disease, or loose stools, to get a C difficile assay. That’s the 1 exception to the rule that we’ve been discussing, which is that in general we shouldn’t just test without clinical thought process going on. A patient with IBD, with loose stools, absolutely needs to be checked because the frequency of C diff in that population is so high.

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 in-box—that’s right, electronically. I’ll see you next time. I’m Dr Peter Salgo. Thanks again for watching.