Peter L. Salgo, MD: In the hospital, if a patient presents with a white count of 50,000, diarrhea, and is really quite ill, probably, Clostridium difficile is going to occur to you. But, coming in de novo to the clinician’s office (someone from the community), how do you suspect Clostridium difficile? Who needs to be tested? How do you make this diagnosis?
Lawrence J. Brandt, MD: I want to make an important point. The most common symptom of Clostridium difficile is diarrhea—non-bloody diarrhea. Blood is only seen in maybe 5% to 8% of cases (something in that range). So, when you have a patient with diarrhea, it’s important to ask certain questions. Those questions are things that we were taught in medical school to help us differentiate whether it’s the small bowel or the large bowel that’s the source of that diarrhea. Small bowel diarrhea usually has generalized abdominal cramps. Large volume diarrhea, colonic diarrhea, tends to have lower abdominal pain, and it has a small volume diarrhea that may contain blood and mucus. It has some rectal symptoms such as urgency and tenesmus. Having said that, the diarrhea of the sick people with Clostridium difficile tends to be very large volume, it doesn’t have blood, and it almost looks like small bowel diarrhea. You can get Clostridium difficile in the small bowel, but primarily, it’s a colonic infection. So, that’s a very important thing.
What questions do you ask a patient about their diarrhea, or what questions should you ask the patient? You should ask them about their diarrhea. You should ask them what the volume is, where their pain is, and if it has blood in it. Almost every patient will tell you that it has a particular smell. Now, I will tell you that I think many patients are valid observers and their diarrhea does smell differently. We all know that there are dogs who can actually go through a hospital, sit at the bedside, and identify someone who has diarrhea from Clostridium difficile because they can smell these volatile aromatic acids in the diarrhea. I will also tell you that I don’t believe that this is a valid point, because maybe 20% to 30% of my patients say, “My Clostridium difficile is back. It’s the same smell it always was.” And when you test them, that’s not the case.
Peter L. Salgo, MD: So, how do you make the diagnosis? What tests do you do?
Lawrence J. Brandt, MD: Well, that depends on what hospital you’re in. There are basically just 2 tests. One is the GDH, glutamate dehydrogenase, which tests for the presence of the organism Clostridium difficile. It doesn’t tell you whether it’s toxin-producing or not.
So, then you need to do a toxin test, and you can either do that by ELISA (enzyme immunoassay) or by PCR (polymerase chain reaction). Some hospitals, mine in particular, do a GDH (glutamate dehydrogenase) test. If that’s negative, they do nothing else. If that’s positive, then they do an ELISA test. If that’s positive, they do nothing else. They call you “Clostridium difficile positive toxin” type. If the ELISA is negative and the GDH is positive, then they do a PCR test.
Peter L. Salgo, MD: Okay. Now, we have patients to whom we give antibiotics and within days; they have diarrhea. Not all of them have Clostridium difficile. A lot of them simply have antibiotic, colonic flora disturbed diarrhea. So, that’s an important differentiation for the clinician out in the community. How do you differentiate that without necessarily going ahead and testing everybody for Clostridium difficile? What do you do?
Lawrence J. Brandt, MD: Well, first of all, I think you should test everybody for Clostridium difficile.
Peter L. Salgo, MD: Fair enough.
Dale N. Gerding, MD: You could stop the antibiotic first. That might solve the problem right away.
Lawrence J. Brandt, MD: If you can stop the antibiotic.
Dale N. Gerding, MD: If you can stop it.
Lawrence J. Brandt, MD: But, I think part of it is, “Does the patient have fever? Does the patient have an elevated white count?”. If the answer to those questions is yes, that patient does not have antibiotic-associated diarrhea—which is just a change in the intestinal bacteria, a change in the way they ferment carbohydrates, and a change in the digestive process. And when you stop the antibiotic, that resolves relatively quickly. It’s not really a sickness; it’s just a condition.
Yoav Golan, MD, MS: A different approach. I must say, there are some antibiotics that are usually associated with gastrointestinal symptoms. Take erythromycin, for example, or azithromycin—some of those are among most of the commonly used antibiotics, and you expect your patient to develop gastrointestinal symptoms. And when they do, you shouldn’t test them. One of the most important principles in testing for Clostridium difficile is that the diarrhea should be unexplained. If you have a good explanation for the diarrhea, perhaps you can wait.
But, you could have a scenario where the patient is doing fine and doesn’t have any other symptoms or signs suggestive of diarrhea. I want to say that one of the issues that we’ve been facing every day, both in the community as well as in the hospital, is over testing for Clostridium difficile. Now, using very sensitive tests, we may be causing additional issues.
Erik Dubberke, MD: I agree. You should only be testing those people that at least have clinically significant diarrhea. So, for 1 or 2 loose bowel movements, you don’t need a test done.
Peter L. Salgo, MD: And that brings up the definition that we all use, perhaps with some artifice. How do you define “mild” versus “moderate” versus “severe” disease? Are there markers? Are there clear-cut guidelines for those terms?
Lawrence J. Brandt, MD: Well, there is certainly for the severe. Severe is classified as patients that have a white count of 15,000, that have an albumin of less than 3, and abdominal tenderness. Those are patients with severe disease. If you talk about complicated disease, then they have the systemic manifestations of disease. They may have a high lactate level. They may have multiple organ failure. They have consequences of the infection that make it complicated.