The Clinical Significance of <i>Clostridium difficile</i> Infections

Peter L. Salgo, MD: Hello, and thank you for joining us for this Peer Exchange^® entitled, “Managing Clostridium Difficile Infections in the Community.” Clostridium difficile infections, which were traditionally considered a top concern for hospitals and long-term care facilities, are increasingly being recognized as a cause of diarrhea in the community setting. Additionally, the community population may lack some of the traditional risk factors, adding to the prevention and management challenges this disease presents. This Peer Exchange^® is comprised of a panel of experts in infectious diseases and gastroenterology. The program will focus on the optimal management of Clostridium difficile infections in the community and will also include a discussion on antimicrobial stewardship.

My name is Dr. Peter Salgo. I’m a professor of medicine and anesthesiology at Columbia University College of Physicians and Surgeons and an associate director of Surgical Intensive Care at New York-Presbyterian Hospital. Joining me for this discussion are Dr. Lawrence Brandt, a professor of medicine and surgery at Albert Einstein College of Medicine and emeritus chief of the Division of Gastroenterology at Montefiore Medical Center in Bronx, New York; Dr. Erik Dubberke, associate professor of medicine at Washington University School of Medicine in St. Louis, Missouri; Dr. Daniel Freedberg, assistant professor of medicine for the Division of Digestive and Liver Diseases at Columbia University in New York, New York; Dr. Dale Gerding, professor of medicine at the Loyola University Chicago Stritch School of Medicine in Maywood, Illinois, and research physician at Edward Hines Jr. VA Hospital in Hines, Illinois; and Dr. Yoav Golan, associate professor of medicine at Tufts University School of Medicine and infectious disease physician at Tufts Medical Center in Boston, Massachusetts. I want to thank all of you for joining us. This is going to be an interesting discussion, I’m sure, so why don’t we jump right in.

We’ve got to discuss, first of all, the bacterium itself: Clostridium difficile. And I want to talk about some of the symptoms associated with this, both in the hospital and in the community setting. Why don’t you start us off, Dr. Golan?

Yoav Golan, MD, MS: Well, Clostridium difficile, as we all know, is an infectious disease that affects the gastrointestinal tract. The most common symptom is diarrhea or loose stools. Many of the patients actually have cramps and fever is not very uncommon. Severe cases can develop sepsis and that can actually deteriorate.

Peter L. Salgo, MD: Do you get septic from Clostridium difficile? Or is that because of transmigration of bacteria across the gut wall?

Yoav Golan, MD, MS: It is confined to the gastrointestinal tract. You usually get septic or you get dehydrated, and you can perforate your colon as a complication as well. The symptoms of those who develop that in the community may be milder on the average, and the likelihood of severe disease in the community is slightly reduced as compared to the disease in the hospitals.

Peter L. Salgo, MD: Why is that? Why would the same bug cause disease that's different in the community versus the disease it causes in hospitalized patients?

Erik Dubberke, MD: Well, I think, to some degree, it depends on which type of “community” Clostridium difficile you’re talking about. So, what Dr. Golan was talking about with the milder symptoms is the community-associated Clostridium difficile, where someone hasn’t had a recent hospitalization. And that population tends to be younger and healthier. When Clostridium difficile causes symptoms, it tends not to be as severe just because they’re younger and healthier, but because they are also able to withstand the Clostridium difficile toxins.

Peter L. Salgo, MD: The patients in my ICU were all there because they’re sick to begin with. Most of them didn’t get to my ICU because it’s surgical because of Clostridium difficile. When Clostridium difficile hits them, it’s a sledge hammer. Is that what you’re implying?

Erik Dubberke, MD: Yes. So older, sicker people have less reserve, just like a bloodstream infection. Someone who is old and sick and gets a bloodstream infection is more likely to end up in the ICU than someone who’s younger and healthier and who ends up with bacteria in the blood.

Lawrence J. Brandt, MD: I want to jump in with just one thing with regard to the concept of sepsis, because we actually studied this. For those who like detail, the 3 most common organisms to account for the sepsis: it was not the Clostridium difficile itself, but it was Klebsiella, E. coli, and Staphylococcus from the skin.

Peter L. Salgo, MD: How does that work? I mean, I can understand E. coli, which is a gut bug. But, why Klebsiella and why Staphylococcus?

Lawrence J. Brandt, MD: It’s a contaminating organism. These are septic. These are people who are usually in the hospital. They’re on antibiotics. It may have just a facilitative kind of a response. I don’t think it’s well understood, but it was a clear top 3.

Peter L. Salgo, MD: That’s fascinating.

Dale N. Gerding, MD: It’s interesting that patients go into shock with Clostridium difficile, but we hardly ever find Clostridium difficile in the blood; it’s almost always absent. But we think what’s happening is that the patients are actually leaking toxin into their circulation. And this toxin, in animal models, has been shown to be a cardio-toxin. That may be the mechanism, but we’ve had a very difficult time documenting that in patients because we don’t have a sensitive enough assay for the toxin in the blood.

Lawrence J. Brandt, MD: And these are not patients who have had 20 or 30 bowel movements a day or patients who can’t get off the toilet and are dehydrated and that’s the mechanism of their shock?

Dale N. Gerding, MD: That’s correct. Their hydration is okay, but they still go into shock.

Peter L. Salgo, MD: But, then you get dehydration leading to shock as well. Fever, dehydration leading to shock, right?

Daniel E. Freedberg, MD, MS: There was a very interesting study that looked at the readmission rates for patients who were hospitalized with Clostridium difficile infection. Compared even among other patients with sepsis, they have the highest rates of readmission of any patients—which I think reflects how sick the underlying substrate is or how sick those groups of patients are.

Yoav Golan, MD, MS: I think this discussion is important, because in the minds of quite a few physicians, Clostridium difficile means diarrhea, but, in fact, the consequences of Clostridium difficile could be pretty bad. The most recent data from the CDC suggest that almost 30,000 Americans die within a month of being diagnosed with Clostridium difficile. Their assessment is that of those, about half are attributable to Clostridium difficile, and that really makes Clostridium difficile one of the more deadly organisms that we get infected with.

Peter L. Salgo, MD: It’s 30,000? So, give me a numerator and the denominator here. In other words, what’s the mortality rate from this disease?

Yoav Golan, MD, MS: Clostridium difficile has not been a reportable infection for a long period of time. Therefore, some of our estimates of incidence may be underrepresenting of the actual occurrence. The most recent data that I know of from the CDC state that about almost half of a million Americans get it. About 30,000 of those who die within a month. So, that’s pretty substantial.

Lawrence J. Brandt, MD: So, if you want a percentage, I think at least based on data from 2011, if you have 350,000 cases per year and you have 30,000 deaths, you’re somewhere around 6.5% or 8.5%.

Peter L. Salgo, MD: That’s enormous, and nobody here mentioned toxic megacolon in all of this. Is that all part of this or is toxic megacolon off in a corner by itself?

Erik Dubberke, MD: Actually, we’ve done some research, where most of these deaths aren’t occurring immediately. You don’t start to see an increase in death until about 30 days after Clostridium difficile infection. And so, again, we’ve been talking about many of these people (with Clostridium difficile) already being sick to start with. Then, Clostridium difficile hits them again. It’s just another physiological insult, but it takes them down a notch. Many of these people are unable to recover after they have additional insult.

Lawrence J. Brandt, MD: That’s the way all the data are reported: 30-day mortality. It’s a very important number.

Peter L. Salgo, MD: Are we attributing their death to Clostridium difficile or is it death associated with Clostridium difficile? It makes a difference.

Dale N. Gerding, MD: About half is directly attributable to Clostridium difficile itself.

Peter L. Salgo, MD: Even so, that’s enormous.

Erik Dubberke, MD: Yes. We’re doing an analysis of the Medicare data and are finding about a 10% attributable death due to Clostridium difficile So, 10% of people with Clostridium difficile are dying because of the Clostridium difficile.

Daniel E. Freedberg, MD, MS: But, also, it’s often very hard to discern the cause of death in these kinds of studies. You know that a patient starts on a spiral, and it can be difficult to determine what initially led to the decomposition.