Peter L. Salgo, MD: Let’s morph this a little bit and talk about who’s at risk. We’ve already talked about patients who come back with recrudescent Clostridium difficile. There is an increased rate, I think it’s safe to say, in community-onset—not necessarily community-acquired—Clostridium difficile. What’s that due to? Where do we go with that?
Lawrence J. Brandt, MD: Well, the community probably represents up to maybe 40% of the infections that we see. I think that that’s a reasonable number, although studies vary on this lower number to about 40%. What’s interesting about the community cases is that they’re occurring in a group of people that were not recognized to be at risk for this disease. We’ll come to risks a little bit later in this discussion, I’m sure, and we’ll talk about the older person and the sick person. But in the community, we’re seeing maybe half of these people who are not on any antibiotics at all, and they’re younger, they’re not older. So, it’s a little bit in contrast to the traditional approach to this disease.
Peter L. Salgo, MD: The mantra was, when I was learning about Clostridium difficile, that it happens in the community, and these are people who get broad-spectrum antibiotics for a long time. Now, they have Clostridium difficile. And you’re telling me it’s not associated all the time with antibiotics?
Lawrence J. Brandt, MD: That’s correct. It is not associated all the time.
Yoav Golan, MD, MS: But we do have to understand that community-associated, community-acquired Clostridium difficile is not very well defined. There is a difference between Clostridium difficile happening in the community versus Clostridium difficile that happens in someone who didn’t have any exposure to healthcare. And this is really important. If you actually look at Clostridium difficile that happens in a community, there are 3 big groups. One group is those people who just got discharged from nursing homes and hospitals.
Peter L. Salgo, MD: So, not healthcare-naïve?
Yoav Golan, MD, MS: They’re not healthcare-naïve. And, in fact, if you look at the healthcare-naïve, the recent data suggest that about 80% of them had some sort of exposure to healthcare within the 12 weeks preceding the occurrence of their disease. To what extent that contributes to their infection is not clear.
Daniel E. Freedberg, MD, MS: I think that also comments on the patients themselves. These are people who, because they’re going to dialysis or because they have chronic comorbid medical conditions, are seeing the doctors frequently. The underlying substrate is just imperfect, and they have a lot of interfaces with the healthcare system.
Peter L. Salgo, MD: And what about people who have Clostridium difficile relatives that are in the hospital? They’ve had Clostridium difficile, they go visit, and then they go home and get sick. Is that considered community-acquired or hospital-related? That’s an important definition, isn’t it?
Lawrence J. Brandt, MD: Yes, it is, but I don’t think that people distinguish between those in the classification systems, and it’s a very important concept.
Peter L. Salgo, MD: And last, out in the community, again, we’re not talking about the people with multiple comorbidities in the ICU. Rather, we are talking about people that simply present with Clostridium difficile. As a group, over time, is this group getting sicker as a group—as a cohort? Or is this community-acquired disease sort of the same over time?
Dale N. Gerding, MD: I think it’s still the same, and it’s generally a much milder disease in the community. The big difference, today, is that when I started in Clostridium difficile, 90% of all cases were diagnosed in the hospital. And then, the length of the stay was 10 days or 14 days. Now, the length of stay is 4 days, and I think what we’re seeing now is procedures being done in ambulatory patients that were done in the hospital previously. Many of these community cases, 80% in fact, have got some kind of ambulatory healthcare contact.
Peter L. Salgo, MD: So, they previously would have been in the hospital, but we’ve discharged them earlier and the Clostridium difficile is the same?
Dale N. Gerding, MD: And 2 things happen to you when you’re seen by healthcare providers. Number 1, you get exposed to antibiotics, more likely, and number 2, healthcare environments are contaminated with spores of Clostridium difficile, so you have a double-whammy. The big mystery, though, is that ambulatory patients who get Clostridium difficile do not have a bona fide antibiotic exposure.
Lawrence J. Brandt, MD: Do you think that the disease is more mild because the disease is more mild or it’s because the person that it occurs in is actually healthier?
Dale N. Gerding, MD: I think it’s because the people it occurs in are healthier. That’s not a uniformly common statement because there are elderly people in the community who do get it—no question about it.
Yoav Golan, MD, MS: I think an important message is that when you see patients who develop Clostridium difficile in a community, as a primary care physician, it doesn’t mean that those people have community-acquired Clostridium difficile. Those could be people who were just discharged from the hospital that have severe disease who can have bad consequences of this disease. And, in fact, a lot of the severe consequences of Clostridium difficile are seen in the community. It’s not community-acquired Clostridium difficile, but it’s still seen and diagnosed in the community.
Peter L. Salgo, MD: Let’s take a look at Clostridium difficile, itself, because everyone thinks of diarrhea, sepsis, potential perforation, and megacolon. But let’s go back to the first principles, if we can. In order to recognize this, we probably should know how it does what it does and how Clostridium difficile affects the intestinal system at a very fundamental level. What’s the problem with this bug?
Erik Dubberke, MD: Just in the last couple of years, we really started to learn about the pathophysiology of Clostridium difficile infection. So, part of it is, what are the important bacteria that protect us against Clostridium difficile? And with more recent sequencing technologies looking at stools and what bacteria are present, it actually looks like non-Clostridium difficile, Clostridium-type species, are very important at protecting us against Clostridium difficile as well as Bacteroides-type bacterium. Exactly why this is, is not clear, but one mechanism may be related to bile acid metabolism. So, when you give antibiotics, you’re altering the bacteria in the gut and then altering the secondary bile acid metabolism from a state that prevents Clostridium difficile germination and proliferation to one that promotes clostridium difficile germination and proliferation.