Epidemiology of <i>C Difficile</i> Infections

Peter Salgo, MD: Let’s talk about some of the epidemiology of the condition, if you will. How common are Clostridium difficile [C. diff] infections in the United States or worldwide?

Darrell S. Pardi, MD: C. diff infections are relatively common. I was just at another meeting, and the presenter said that C. diff is rare. I challenged her. I asked, “Why are we talking about it then?” Her point was that it’s rare, from an FDA definition perspective. So it qualifies for special consideration at the FDA.

For clinicians, especially hospital-based clinicians, C. diff is all too common.

Peter Salgo, MD: Is it getting more common or less common? And what’s this NAP1 strain anyway?

Darrell S. Pardi, MD: The change in epidemiology is interesting. Through the 1990s and early 2000s, there was a significant rise in the United States. And since about 2010 or so, it’s plateaued. But it plateaued at a high rate.

Peter Salgo, MD: So, it’s not good to be at a plateau if the plateau is at 20,000 feet, I guess?

Darrell S. Pardi, MD: The estimate is that there are about 500,000 cases in the United States per year.

Peter Salgo, MD: Well, that’s not rare. Where I come from, that’s a lot.

Dale N. Gerding, MD: Right. C. diff is actually the No. 1 healthcare facility—associated infectious organism, to date, displacing Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. This is new. This is something that has occurred, progressively, for the last 15 years or so. And this NAP1 strain that you mentioned is really critical, in terms of driving that increase in rates, especially in healthcare institutions. It’s not as prevalent in the community. However, it’s now on the decline, which is the good news. We’ve seen hospitals that had a 30% to 50% rate of NAP1 strains decrease to probably closer to 20%.

Peter Salgo, MD: Is NAP1 more virulent or is it simply a different strain?

Dale N. Gerding, MD: Both. It is more virulent, I believe, although there is some question about that in the literature. We find that a higher proportion of these patients who have NAP1 have really severe and fulminant disease. But you could have NAP1 asymptomatically. You could have it with mild disease expression or you could have extremely severe disease. It covers the spectrum. It’s important to remember that not everyone with NAP1 is going to be deathly ill. It’s a complete spectrum. But it has a third toxin, this binary toxin, that probably is an important pathogenicity factor.

Yoav Golan, MD: I think it’s important to remember that what has changed with C. diff is not just the frequency, but the severity. Many will argue that C. diff, in the past 20 years, is somewhat a different disease from what it used to be.

Peter Salgo, MD: How so?

Yoav Golan, MD: Not only do we have strains that are more infectious, but, as you heard, we also have strains that are more likely to make the person very sick. I think that this increased severity of illness has contributed to the increased appreciation of C. diff being a major healthcare pathogen.

Peter Salgo, MD: Since you bring that up, let’s go right to the morbidity and mortality. How big of a problem is this, from the perspective of people being sick for a long time and/or dying?

Yoav Golan, MD: When you discuss epidemiology, it’s important to remember that unlike tuberculosis and other infections that have been reportable for a very long period of time, C. diff only became reportable a couple of years ago. I think we are just starting to understand the epidemiology, and I think there was a lot of underappreciation as to how common C. diff is. If you look at the CDC [Centers for Disease Control and Prevention] website, when the CDC was still citing about 400,000 annual cases—this was a few years ago&mdash;they also reported that about 30,000 people die, if I’m correct with the numbers, within a month of being diagnosed with C. diff. And it’s not necessarily because the C. diff is out of control. But, as you know, you get C. diff. You’re older, you have comorbidities, your comorbidities exacerbate, and you end up dying or getting admitted to the hospital. So, I think the consequences are not just related to how common it is, but to how commonly it exacerbates your comorbidities. And with the host becoming older nowadays, with more comorbidities, the consequences of C. diff are worse as well.

Peter Salgo, MD: So, the people who are at highest risk, is it just everybody who’s had antibiotics? Who’s at highest risk?

Darrell S. Pardi, MD: Highest-risk patients are older patients, in the hospital for long periods of time, who are on antibiotics.

Peter Salgo, MD: Those are all the bullet points. Is it more likely that if you’ve had a C. diff infection that you’re going to have another? Does that put you at high risk?

Dale N. Gerding, MD: It certainly does.

Peter Salgo, MD: So, we’ll add that to the bullet points: antibiotics, older, hospitalized, previous C. diff. What about C. diff in the household? Somebody else in your household has had C. diff.

Darrell S. Pardi, MD: There is actually an interesting study on this concept of community-acquired C. diff. It changes the way that we think about the infection. We used to think of it as an inpatient infection in older patients, etc. But now, multiple studies have shown that a significant proportion of C. diff occurs in outpatients, some of whom have hospital exposure. There was a study that looked at the infection rates in household dwellers of patients who were discharged with a diagnosis of C. diff compared with those discharged from the same hospital without C. diff. The attack rate was something like 70-fold higher in spouses, if their spouse had been discharged with a diagnosis of C. diff.

Yoav Golan, MD: I was just involved in a case in which a person received clindamycin, from a dentist, for a tooth abscess. About a week-and-a-half later, the patient developed C. diff that was so bad that he had to be admitted to the hospital and had to undergo a total colectomy. What was interesting is that his wife was in a skilled nursing home. Although she was not sick, I always thought that she was the source for the C. diff. She may be carrying the C. diff.

Peter Salgo, MD: When I was a young house officer, clindamycin was the first thing that we talked about. We didn’t even call it C. diff, right? It was pseudomembranous colitis. Is it still a big offender? Is clindamycin still the drug to avoid?

Dale N. Gerding, MD: Clindamycin is the highest-risk drug, I believe. However, the use of clindamycin has declined markedly from when it was first marketed. It remains to be a very effective drug for treating methicillin-resistant Staphylococcus aureus in the community setting. So, it has considerable outpatient use. Oral surgeons and dentists use it frequently for dental abscess treatment.

Peter Salgo, MD: I remember this line from a movie: “Be afraid, be very afraid.” That’s an offender, if you will.

Darrell S. Pardi, MD: I think the dentists are getting that message, and I think they’re using it less than they used to. But, in addition to clindamycin, drugs like fluoroquinolones, which are used very commonly, used to be thought of as a low-risk antibiotic. They are now recognized as a high-risk class of antibiotics.

Peter Salgo, MD: But everybody takes a Z-pak [azithromycin].

Dale N. Gerding, MD: My wife went to the dentist. She had a dental abscess. She came home with a prescription for clindamycin plus Florastor. I looked at that and I said, “You’re not going to take that.” I wrote her a prescription for ampicillin, and she took that. It’s still a risk, but it’s a much-lower-risk drug.

Transcript edited for clarity.