Factors That Impact Clostridium Difficile Infection Recurrence

Lawrence J. Brandt, MD: I want Erik to comment on the reevaluation of these patients.

Peter L. Salgo, MD: That’s what I’m trying to drive at.

Lawrence J. Brandt, MD: You taught me about the fact that you can have toxin in the stool for an extended period of time after the index episode. And, therefore, I’m not really sure how to reevaluate those patients. So, teach me how to do it.

Erik Dubberke, MD: Unfortunately, many people are not informed that Clostridium difficile could come back. And lots of those people, where it does come back, end up in the hospital just because diarrhea came back—they didn’t know to call someone, it gets worse and worse and worse, they end up in the hospital.

The first thing to do, if it’s someone post discharge, is to educate them before they’re discharged that it might come back. And, as far as if it does come back, if you get that call, again, the first thing I ask is, “How severe is your diarrhea? Are you having any other symptoms?”

If they’re just having 1 or 2 loose bowel movements a day, I say, “Well, let’s hold off. Let’s wait a little bit. If it gets worse, give us a call.” But if they’re going 3, 4, 5 times a day without another explanation, if they’re having fever or a lot of cramping, I’ll go ahead and test them. I prefer toxin testing because it’s more specific for a Clostridium difficile infection. You’re less likely to get an asymptomatic carriage, which you can get with a PCR (polymerase chain reaction)—based test that many of these people post Clostridium difficile will get. You could detect shedding, again, after the Clostridium difficile resolves. But, unfortunately, the clinician often does not have a choice in regard to what test is performed. The lab they go to performs whatever test the lab performs. So, some of it is, also, in understanding what type of testing is being done and to take that into context when you’re testing the patient. And if it’s positive, I talk to the patient. Again, I don’t automatically treat. For some people with true Clostridium difficile infection, it will go away on its own. And actually, they’re less likely to have a recurrence if you don’t treat them.

Yoav Golan, MD, MS: This brings an important point, though, which has to do with testing someone who just recovered from a Clostridium difficile episode. For a long period of time, we actually requested that we would like to transfer a patient to a rehab or nursing home. And we’ll be requested to test a patient who is now clear of Clostridium difficile. And we do know that after you’ve been treated successfully for Clostridium difficile, you still carry those spores, and those spores are probably the reservoir from which your recurrence will emerge. You can be tested positive, so it is important to stress that no routine testing should be done in people who responded to therapy. It’s only for people who re-develop symptoms that are worse and in instances that look like their episode actually should be tested. What Erik is saying is that the decision of who to test for Clostridium difficile has really become an important decision and one should not just test based on the patient and the severity of their symptoms.

Peter L. Salgo, MD: Let me ask a couple of very simple questions. Why, once you’ve cleared this infection with antibiotics, do people recrudesce?

Yoav Golan, MD, MS: You already mentioned that Clostridium difficile is a nightmare-type of pathogen, and I would agree with that. And one of the reasons it’s a nightmare-type of pathogen is because it has a form, actually 2 forms, and one of the forms is the spore form. We all know about anthrax spores and others. We know that spores are very hardy and survive in the environment. We also know that they survive acid. Spores are also not susceptible to antibiotics. So, when you treat someone with Clostridium difficile who got infected with Clostridium difficile and has a large amount of spores in their gastrointestinal tract, the antibiotics don’t really affect the spores—they affect the vegetative form of the bacteria, the form that divides and produces toxin. You get better with antibiotics because the disease-causing form is eliminated, but you remain colonized with multiple spores. Those spores may be dormant for a period of time, but then when you take the antibiotics away, those spores will germinate again. Bacteria will come out and vegetative cells will divide and produce a toxin. So, this spore reservoir is problematic because it can give you your recurrence and it’s also the vehicle that may infect other people. It is important to remember that the person with Clostridium difficile serves as the source from which other patients will get infected.

Lawrence J. Brandt, MD: That’s a very important point. But the other part of that is that the reason that you might have gotten the Clostridium difficile in the first place is maybe that—not for one episode, but for multiple recurrences—your intestinal biome is not normal and vancomycin does not cure your intestinal microbiome. So, you’re starting from square one again, and unless you can correct that, if you have an abnormality and it’s not corrected, you’re going to be one of those people that just doesn’t get better.

Peter L. Salgo, MD: So, the same thing that gave you Clostridium difficile the first time is going to put you at risk for getting it again?

Lawrence J. Brandt, MD: Yes, except there’s a little bit of a gray zone here, because the intestinal microbiome for patients that only have one episode is not substantively different from normal. It’s only abnormal with recurrent disease.

Peter L. Salgo, MD: Do you recur with the same strain or do you recur with different strains?

Yoav Golan, MD, MS: Well, that’s a very good question. Many of those who have a recurrence have the same strain as the initial episode, but there have been more and more descriptions of people who have a diversity of strains. That’s not only applying to recurrence, where you can have a strain that was actually different than the strain that causes the first episode, but also for those who have 1 episode of Clostridium difficile. You may sometimes, if you really look carefully, find several strains. So, this is a really important question. It is hard to answer and may not really matter that much, in fact. But there is diversity of Clostridium difficile—not just in the environment, but sometimes in our gastrointestinal tract as well.

Dale N. Gerding, MD: It probably depends on how long it’s been since your previous episode. The longer it is, the more likely you are to have a different strain. We looked at patients within 28 days of their previous episode, and about 80% of them had the same strain that caused the original episode. We have found, though, that as many as 50% might have new strains, depending on how long you follow patients.

Transcript edited for clarity.