An overview of the risk factors that contribute to the development of Clostridioides difficile infection in various health care settings.
James A. McKinnell, MD: One of the things that is helpful to understand is, among the spectrum of disease between health care-associated and community-onset cases, are there subsections of these groups of patients that are at higher risk for either developing disease or really bad outcomes?
Kelly R. Reveles, PharmD, PhD, BCPS: Yes, from a healthcare-associated standpoint, we are typically looking at patients who have already come into the hospital, they already have underlying illnesses. Maybe they’re in intensive care for a critical illness. Those patients are going to be the ones who we really worry about in terms of high mortality rates. There are some data to suggest that for patients in the ICU [intensive care unit], mortality may be as high as 37%, in critically ill patients with Clostridioides difficile. So again, really severe outcomes. Now, community-associated C diff has been a little bit tricky. Of course, antibiotic exposure can potentially increase risk. We think that maybe an increased use of gastric acid suppressants among our outpatients may have contributed to that increase in community-associated cases. But as a general rule of thumb, our community-associated patients tend to have better outcomes and tend to have less severe disease compared to our health care-associated cases.
James A. McKinnell, MD: Any comment on patients in nursing homes?
Sahil Khanna, MBBS, MS: I’ll add to that. Nursing homes are notorious to harbor patients with C diff infection. There have been outbreaks reported. Also, patients in nursing homes are exposed to antibiotics frequently, are exposed to PPIs [proton pump inhibitors] frequently. The incidence has been stable, but you do see high, stable incidence in patients in nursing homes, and they tend to have adverse outcomes in a similar manner to the hospital-acquired patient population, where they tend to get admitted to the hospital fairly frequently with C diff infection. I’d like to add one more thing to what Kelly said. In terms of the community-acquired patient population, there’s a small group, roughly about 20%, who have not been exposed to antibiotics. From a clinician’s standpoint, if you’re seeing someone who’s a little younger, because community-acquired patients are younger, who comes with chronic diarrhea lasting over several days to weeks, and they don’t have antibiotic exposure and there is no other explanation for the diarrhea, do consider C diff infection in today’s world because you could be missing that if you’re only looking for the hospitalized patient who’s had antibiotics. Because studies after studies are showing that C diff is out in the community in younger patients who may not have even received antibiotics.
James A. McKinnell, MD: Carl, talk to me about outpatient C diff. What are you seeing in that realm, if any at all?
Carl V. Crawford, MD: What we’ve pointed out was where this C diff really comes from. A lot of these places such as hospital care centers or nursing homes are just reservoirs where C diff exists. But as I was mentioning before, C diff is a ubiquitous organism, and it’s in the environment. In order for these patients in the community to get a C diff infection, they have to pick it up from somewhere. They may be picking it up from the food supply. They may be picking it up after being in the same local environment as someone who had C diff, who was discharged from the hospital. It’s difficult to predict which patients are going to be truly harboring or being colonized by C diff in the community, but we know that it can range anywhere from 3% to 6% inside of the community. It’s just a matter of setting up the right sort of perfect storm.
We mentioned that antibiotics are a big risk factor for developing C diff, but we can’t forget about the role of the diet that we mentioned earlier and what are a lot of the patients in the community consuming? Are they eating a healthy diet that nourishes the microbiome and supporting the protective mechanisms of colonization resistance from firmicutes and bacteroidetes? Are they consuming things that we never thought about before, such as complementary alternative medicines, things that are over the counter, like herbs and supplements and special kinds of teas, that also we know have some antibacterial activity? There are a lot of different things to consider when we see this increase slowly happening inside of the community, and it’s an active area of investigation that is important for us to understand, just given the numbers of what we’re seeing rise inside of the community. Of course, the patients inside of the hospital are just naturally sicker, and they tend to do worse than our patients who are in the community who can function and be in the community, so they have more of a reserve. They may have more resilience in their microbiome to attenuate the disease in the community.
James A. McKinnell, MD: How do we think about the interplay between exposure to C diff spores, antimicrobial stewardship, and this diet change? How do these things balance out?
Sahil Khanna, MBBS, MS: Jim, in my mind, what I think about is, what’s the highest risk factor? Apart from that, what are modifiable and nonmodifiable risk factors? The highest risk factor, as we all know, is antimicrobial exposure. Antimicrobial stewardship is where you get your best bang for the buck, especially if you’ve got a patient population who’s getting frequent antibiotics, maybe for reasons that are not completely clear. People getting antibiotics for viral infections, which we’ve seen recently in the pandemic. That’s one part of it. Then I think about what are modifiable versus nonmodifiable risk factors? Increasing age is a risk factor for C diff that is nonmodifiable, sometimes hospitalization is nonmodifiable, and other disease states, those are nonmodifiable. You have to work around them, but antibiotics and antibiotic exposure probably is the most important modifiable risk factor that we have around for C diff.
Kelly R. Reveles, PharmD, PhD, BCPS: It’s important to note that not all antibiotics are created equal, and when we think of C diff risk, we tend to think of antibiotics that are going to have the biggest impact on our gut microbiome. It’s going to be related to spectrum activity, pharmacokinetics, are we getting concentrations in the gut, and then total exposure. Clindamycin has been our prototypical antibiotic to increase C diff for us because it has broad anaerobic coverage, high concentrations in the gut. But there are definitely several other classes of antibiotics that we know are associated with increased risk, like the carbapenems, our later-generation cephalosporins, our third and fourth generation. Some of our extended-spectrum beta-lactamase inhibitors like piperacillin/tazobactam, which just about everybody in the hospital gets nowadays, ampicillin/sulbactam, and then fluoroquinolones. Again, coming back, although a single dose can increase our risk for C diff, it’s cumulative antibiotics exposure that predominantly increases risk, the total duration of therapy, total number of different antibiotics, and dosing frequency as well.
James A. McKinnell, MD: On the duration of antibiotic question, the traditional teaching that we’ve heard is 7 days is kind of your cutoff. If you can keep it less than 7, your risk of C diff is [less] than more than 7. How would you react to that?
Kelly R. Reveles, PharmD, PhD, BCPS: From a stewardship standpoint nowadays, we are looking to see how short of a duration of therapy can we treat a patient with, to where we still optimize outcomes but limit duration of therapy just for this reason, to help not only prevent C diff but the development of antimicrobial resistance. It totally depends on the patient. We have uncomplicated UTIs [urinary tract infections] that can be treated for a few days and be OK. But then we get some more complicated infections or septic patients with bacteremia where we need longer durations of therapy. It’s just that balance of treating the patient. Although we say antibiotics are modifiable, they are still critical for treating infection. It’s just a matter of, can we potentially use alternative antibiotics that pose a lower risk for C diff and/or decrease our duration of therapy without affecting patient outcomes?
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