 titled, “Expert Perspectives on Advances in the Management of 

.” I am Peter Salgo from the Columbia University Irving Medical Center in New York, New York. Joining me in this discussion areTeena Choprafrom Wayne State University School of Medicine in Detroit, Michigan;Paul Feuerstadt from the Yale New Haven Hospital in New Haven, Connecticut;Dale Gerding from the [Edward Hines Jr] Veterans Affairs Hospital in Chicago, Illinois;Thomas Lodise from the Albany College of Pharmacy and Health Sciences in Albany, New York; and Joseph Reilly from the AtlantiCare Regional Medical Center in Galloway, New Jersey.Our discussion is going to focus on the standard of care as well as some shifting paradigms in the management of initial and recurrent 

 infections. I want to welcome all of you. Let’s get started.Let’s ask the obvious and basic question: Why is 

 such an important issue? Who wants to start? Dr Chopra?

 is a huge burden on the health care system, and it is the most important cause of hospital acquired diarrhea. Hence it’s very important that we think about the epidemiology of 

 and how it changes. It causes a huge economic burden and also is responsible for very high morbidity. On top of it I always consider C 

 as a nuisance disease. I think it makes a patient more prone to recurrence, which is very debilitating for the patient. I’ve had patients who’ve had recurrent disease, and they’ve had to lose jobs because of the nuisance it causes with the diarrhea they experience. So this is a reason why 

It sounds simple, right? And if you describe 

 to the public, they say, “It’s a diarrheal illness,” and they say, “So what, it’s diarrhea.” It’s not, and I see 

 all the time. Paul, you’re nodding. How do you explain the impact of this disease? It’s big.

 The impact is huge. In fact, in 2017 it was estimated that 365,200 Americans were affected with 

 infection, which is a really remarkable number. You know, 

 is an interesting organism. It’s a gram-positive spore forming anaerobic rod, and it works in a couple of ways. There 2 phases of the infection: The spore phase and the vegetative phase. And the vegetative phase is the phase that most of us think about when we think about 

 infection, because that’s the phase that releases toxin A and toxin B to stimulate the diarrheal syndrome associated with it. But importantly, the spore phase is also a really essential phase because it is much hardier. It’s like a cocoon and protects the 

 as it spreads from individual to individual. That’s the phase that really results in outbreaks of this infection.

 When my hospital, several years ago, switched over to putting Purell or other antimicrobial dispensers all over my ICU [intensive care unit], my concern was that people were going to use them in lieu of handwashing. The 1 takeaway for all the residents, nurses, and PAs [physician assistants] was that it doesn’t work on the spore phase. Does it, Paul?

 No, it doesn’t. In fact, that’s an excellent point. The spore phase is resistant to gastric acid and alcohol-based hand sanitizers like Purell. When we swallow the spore phase, it can get through our gastric acid, it gets to our small bowel. In the small bowel there’s a convergence to the vegetative phase, where the vegetative phase multiplies, divides, and multiplies some more. It really builds an army heading toward the colon. But I’m a gastroenterologist, and I think the colon is a brilliant organ. And the colon is a really smart organ because the colon has its own defense system independent of the blood-borne defense system that protects it. That defense system is colonization-resistance for the microbiota.

 We’ll get to that. But what are the main virulence factors? All 

 infections are bad, but are some worse than others? How do we know this? Who wants to tackle that? Paul, do you want to start?

 Sure. What are some risk factors? The risk factors I like to think about are 3-fold. I think about demographics, medication exposures, and environment. From a demographic standpoint: anybody over the age of 65 years old, female gender; any form of immune compromise: chronic kidney disease, HIV, inflammatory bowel disease, inflammatory bowel disease on a biologic; medications: antimicrobials are at the top of the list, proton pump inhibitors, histamine blockers; environmentally: people who live in skilled nursing facilities, people who spend significant amounts of time in the hospital. Those individuals are all at remarkably increased risk of 

 Right. I don’t want to skip over the virulence factors, if there are any differences, 1 

 compared with another. You said there’s toxin A and toxin B. Do some 

 produce only A and some produce only B? Does every 

 produce all the toxins? Who wants to weigh in on that? Help me out.

—you know in the 1990s we had the North American strain, and that 1 strain caused huge outbreaks in North America and Canada. This is the strain we are really worried about because it produces huge amounts, 10 to 16 times the amount of toxin A and toxin B, and also a binary toxin. So these toxigenic strains are more worrisome because they’re also responsible for outbreaks and huge transmission inside the hospital setting, and even in the community setting.

If you enjoyed this content, you should subscribe. We have an e-newsletter, and you can receive upcoming 

 and other great content in your in-box—that’s right, electronically. I’ll see you next time. I’m Dr Peter Salgo. Thanks again for watching.

C. Difficile Risk Factors and Manifestation

. Does it matter clinically if you make that distinction if the patient has diarrheal illness? Dale, does it matter?

It sure does. The strains have been epidemic since the turn of the 21st century. The so-called 027 strain and the 07A strain have higher mortality associated with them. By the way, this is not a benign diarrhea. Patients are usually older. Many of them don’t tolerate it, and the mortality can easily exceed 5% So these strains of toxin are very lethal, especially in older patients.

I want to stop you because that is a shocking number: 5%. That is an enormous mortality figure. Is it because the bacterium—or whatever you want to call it; I guess it’s a bacterium—is a bad bacterium or because the population that it affects is so susceptible and immunocompromised? [The patients are] often old, often debilitated. What do you think?

 It’s a combination of both. There are lots of papers out there that say there is and there isn’t a difference in the mortality of the 027 strain. Most of them think there is a difference, and it’s a higher mortality. But this strain is also associated with infecting older people much more commonly than younger people. You can’t get away from the fact that the older people are more susceptible and are likely to be immunocompromised and likely to have higher mortality.

Yeah, people are fond of saying that 70 is the new 40, but not necessarily the [patients with] 

 Often people in their 80s and 90s have the highest mortality.

 We see that a lot at the VA [Edward Hines Jr Veterans Affairs Hospital] too. I think Dale can attest to this when we think about some of the statistics with 

. Once you get past 65 years old, you see a substantial increase in mortality and estimate at 1 of 10. You see this linear curve, but that goes up with age, particularly individuals who get the epidemic strain.

 Come back to that number again. These numbers—I knew them, but I’m hearing them again, and they’re scaring me. Over 65 the mortality is 10%, 1 of 10?

That is higher than what we’re seeing with COVID-19 [coronavirus disease 2019] right now. Yet nobody is speaking about this the way we’re speaking. I understand why, but this is a disease that is killing people.

That’s why it’s labeled as an urgent threat by the CDC [Centers for Disease Control and Prevention], because of the high mortality and morbidity. One important thing we should also remember is the changing epidemiology. We are seeing over the years that the hospital-acquired 

has sort of plateaued. But the community-onset 

 is on the right because of the poor antibiotics we have in our community. We have good stewardship programs in the hospital, but we don’t have as strong stewardship programs in the community. Community on set 

Strains of C. Difficile

 for a moment. What are the risk factors in the community, and how do they differ in the community- vs the hospital-based populations? Dale, do you want to start us on that?

That’s a really good question because there’s 2 factors that we need to have in order to get 

. One is antibiotic use, and the other is exposure to the spores. So the spores are ubiquitous. They are in the environment, and they even contaminate at a very low level some foods, meats, root vegetables, and lettuce. Those are probably how patients in the community get exposed.On the other hand, when the CDC [Centers for Disease Control and Prevention] has looked at community-associated 

 they found that about 80% of these patients have had an exposure to health care as an outpatient. So it’s doctor’s office, dental office, and chronic dialysis units, ambulatory surgery. This is where you have 2 risks. One is that somebody is going to give you an antibiotic. Those are called “doctors.” [Laughter.] They put people at risk of 

. The other exposure is that the health care environment is more contaminated with 

 spores than is the environment outside health care.

It’s not just the people who are in the health care system. It’s not just the people who got the antibiotics. They go home, they’ve got spores, and then their families are exposed. It seems to me that that’s part of the issue, isn’t it?

Those spores can live for a significant period of time on many surfaces, even when exposed to sunlight. You’ll see some data that say, “Alcohol and certain products can kill the spores,” but they really have to be used properly, where the liquid sits on a surface for a significant period of time to have effects. The fact that the spores can be taken home with you on your lab coat and in your house and on surfaces for 6 months, a year, or longer certainly put people at risk.

Managing Community-Onset C. Difficile

Let’s change gears a little. We’ve been talking about community-onset 

[CDI], and we’re talking about in-hospital 

. But there’s another syndrome entirely, which is recurrent 

. How do you define that, and what does that really mean, Joe?

, if you think about it, the nature of the disease is that about 1 of 4 or 1 of 5 patients who with 

 wind up getting it back within 30 or 60 days of being treated initially. We have patients who get recurrent disease again and again. If we saw 100 patients with 

 and we treated them all successfully, about 25 patients would come back with their first recurrence. If we treated those 25 successfully, about 40% of those patients would come back with their second recurrence. And if we treated those patients successfully, about 60% would come back for their third recurrence. So for every 100 patients we treat, you wind up treating over 140, which is the nature of the beast. That’s assuming that there’s no mortality.

Holy smokes. That’s a nasty nature. We know this, and we see this. But it’s certainly something to contemplate. This disease just hangs in there.

Dr. Salgo, before we go on I want to say 1 thing. We mentioned some of the risk factors, and we keep on talking about antibiotics, so it’s important to remind our audience that not all antibiotics are treated equally. Time at risk, as Dale said, is a major risk factor. In the community setting, even going to the dentist could put you at risk for CDI. But being in the hospital, the longer you are, the greater your risk is.

When we think about antibiotics, the antibiotics we use most—fluoroquinolones, third-generation cephalosporins—are the drugs listed at the top of our guidelines that actually have a greater risk for selecting for a CDI infection relative to other drugs. I think about piperacillin-tazobactam, a drug that we use frequently, we always think about the beta lactamase inhibitors having a lower risk, but they still carry a great risk.

Teena talked a lot about stewardship. One thing I would say with antibiotics is that every day matters. Even 1 dose of an antibiotic can put a patient at a greater risk for CDI relative to no antibiotics. That risk increases substantially after 3 days of antibiotics. The 1 thing we always talk about when we talk to teams—they’re like, “Let’s just keep the antibiotics on for 1 or 2 more days. Let’s just be certain.”

In a hospital—Dale, if we think about our VA [Edward Hines Jr Veterans Affairs Hospital] patients, 70, 80 years old, high risk of mortality, high risk of morbidity and recurrences—often the worst thing you can do in a lot of our patients is to continue them on an antibiotic without an indication. Because that risk of CDI persists in that patient for at least 3 months. Again, the risk is great as you know during the first 14 days or 30 days, but even so, if you look at some of the better data, they carried a heightened risk of developing a CDI infection for 90 days.

We talk about stewardship, and the 1 thing we always do in our institution [Albany College of Pharmacy and Health Sciences] is drive home messages to get people off antibiotics, get them off the broad spectrum ones. We play up CDI, and Teena highlighted all morbidity and mortality associated with the disease.

Before we change gears, I want to talk about the effect of recurrent CDI on a patient’s life. It’s 1 thing to have a terrible diarrheal disease and somehow or other you get through it and we can fix it. Then you come back; the story of recurrent diarrheal illnesses is terrible. How does it affect a person? Paul, if you could, how does that affect the entire health care resource in this country? This is a significant illness.

It’s very significant. The burden of this disease is quite tremendous. We are seeing patients like this frequently. Not only the physical manifestations—the abdominal cramps, the diarrhea, the dehydration, potential syncope as a result of the frequency of the loose stools—but also the psychological effects, the adaptation or relational; the productivity effects. Patients look you in the eye, and they say, “I can’t go to work, I still can’t go to work.”

What we did was we set up a study in which patients with active 

—and patients with a distant history of 

—simply filled out a survey. We looked at 350 individuals. One-third of them had active infections; two-thirds of them had a history of infection; and across the board [there was] psychological impact, adaptational, relational, and physical. Clinical symptomatology and productivity were impacted greater than 50%, both active infections and also with a distant history.

One of the concepts that is very important is to acknowledge for patients is that this is real and that what they’re going through is not just them. I had a patient just today who contacted me for a third opinion and I immediately said, “Look, I’m here to help you, and I’m going to help you get better from 

.” And 30 seconds into the conversation she started crying. That was impactful. I said to her immediately, “It’s OK. You’re not alone. I see quite a few people in a similar circumstance. People feel stressed about this. They have post-traumatic stress disorder; they feel anxiety or depression. Sometimes they feel like they can’t be the person they were before. Educating ourselves as clinicians about this disease, both the physical manifestations and the emotional manifestations, will make all of us better clinicians and better equipped to approach these individuals and help them get better physically and emotionally.

Right. To get to that point, though, you’ve got to make the diagnosis. Let’s take a look really quickly.

I just want to make 1 point about these older individuals and recurrent-disease and long-term care settings. You talked about the impact of recurrent disease in older adults who are residing in long-term-care settings. When they keep getting admitted to acute hospitals with recurrent 

, they also develop coinfections within MDROs [multidrug-resistant organisms]. The downstream effects of being admitted to the hospital are huge on the health care system.

It is even worse for these older individuals.

Right. It’s a disease we don’t have a good enough handle on, at least not yet.

Expert Perspectives on Advances in the Management of C. difficile

C. Difficile Risk Factors and Manifestation

Strains of C. Difficile

Managing Community-Onset C. Difficile

Recurrent C. Difficile

C. Difficile: A Differential Diagnosis

Testing for C. Difficile Infections

Screening for C. Difficile

C. Difficile: Clinical Practice Guidelines and Treatment Options

C. Difficile: Updates to Clinical Practice Guidelines

Selecting Therapy to Treat C. Difficile

C. Difficile Treatment: Fidaxomicin

Choosing Between Vancomycin and Fidaxomicin for C. Difficile Infections

C. Difficile Treatment: Bezlotoxumab

Preventing/Treating C. Difficile: Unmet Needs

Fecal Microbiota Transplantation for C. Difficile Infections

Emerging Treatment Options for C. Difficile Infections

C. Difficile: Barriers Treating With FMT

Making Strides in the Management of C. Difficile