The Relationship Between the Gut Microbiome and Management of C. Difficile - Episode 7
Identification and Management of Recurrent C Difficile Infection
Shared insight on the prevalence of recurring Clostridioides difficile infection and management strategies.
James A. McKinnell, MD: When we talk about patients who are immuno-suppressed or have dysregulated gut microbiomes, and they get C diff [Clostridioides difficile] and then get it again, what’s the syndrome of recurring C diff? What’s your affinity for this? Is this a disease you like to treat? Or does it drive you crazy?
Carl V. Crawford, MD: This is 1 of the most frustrating aspects of this infection. We hope that when someone comes in with pneumonia, we can treat with a round of antibiotics. But when I see a patient, I must tell them that there’s a chance that this infection may come back. After a first episode of C diff infection, I tell my patient they have about a 20% chance that it’s going to come back.
James A. McKinnell, MD: I want you to see the numbers people quote. You say 20%. What do you guys say?
Sahil Khanna, MBBS, MS: I’d say between 20% and 30%, depending on overall risk factors that they have for recurrence after the first infection.
James A. McKinnell, MD: Kelly?
Kelly R. Reveles, PharmD, PhD, BCPS: Usually 20% to 25%. It’s going to depend on what they were treated with in the first place, though. We can get to that later, but I usually say about a quarter because that’s a nice round number.
James A. McKinnell, MD: Maybe I’m more generous. I say about 30%.
Carl V. Crawford, MD: It slowly increases over time. After they get a second infection—if they’re in that 20% who got a second infection—they probably have a higher chance of getting it again. I’ll say about 40% or so. If they did get another infection after that, then they have about a 60% chance of getting it again. I consider them having a greater chance in a flip of a coin than getting C diff. That’s what I call the vicious cycle of occurrence that we see thrown around, and it’s written in papers all the time. The reason is those individuals may have been treated with antibiotics or other agents to the point where they have lost resilience in the gut biodiversity and the microbiome. C diff will flourish in that environment. Although we’re throwing the antibiotics to diminish the vegetative forms, we’re not addressing the spores that are present in this dysbiotic state. As Dr Khanna had mentioned, C diff is very good at producing its own bacteriocins or chemicals that suppress the recovery of that biodiversity. C diff is extremely efficient at camping out and remaining inside a person’s gastrointestinal tract.
James A. McKinnell, MD: Is this where diet plays a role? Should you eat more complex fibers?
Carl V. Crawford, MD: Early on you want to maintain the best balance inside of the gastrointestinal tract that you can. But over time, you reach this point of no return, which is that vicious cycle of recurrence because the microbiota have been shifted in such a way that you’ve lost the ability for colonization resistance to come back on its own. As we were talking about earlier, in treating C diff appropriately, the first go-round has an incredible impact on the risk of a subsequent recurrence. We’ll talk about IDSA [Infectious Diseases Society of America] guidelines in a few, and we’ll talk about why there have been shifts over the last decade or so in order for us to optimize treatment to treat our patients adequately and optimally the first time around because that gives them the best chance of success.
James A. McKinnell, MD: Let’s jump into that. What’s the best treatment for the initial phase, and what’s the best treatment for the second?
Sahil Khanna, MBBS, MS: It’s interesting when you use the word best. That’s important.
James A. McKinnell, MD: Chosen specifically. There was a reason for that.
Sahil Khanna, MBBS, MS: When I treat a patient who has C diff infection, I look at many things. I make an accurate diagnosis. They have the risk factors, they have symptoms, they have a test to confirm that this person does have C diff infection. After all that housekeeping stuff is done, I start looking at what does this patient have that’s going to increase this person’s risk of recurrence? If I see a person who has an increased risk of recurrent C diff by risk factors such as increasing age, immunosuppression, having a severe infection, getting other concomitant antimicrobial therapy at the same time—meaning they have the pneumonia still being treated and they have C diff at the same time—then I look at the IDSA guidelines. I think about using a microbiome-sparing therapy, such as fidaxomicin for a period of about 10 days, or sometimes they use the extended regimen for about 25 days—the same number of capsules. But I try to use that in a patient who has the increased risk of recurrence. Cost is an issue. Availability is an issue. If either of those is an issue, then you must flip to vancomycin. If you have someone who doesn’t have these traditional risk factors for recurrent infection, then you can use vancomycin. This is the second-best treatment in most situations for the first infection. Again, it’s a 10-day course.
James A. McKinnell, MD: Kelly?
Kelly R. Reveles, PharmD, PhD, BCPS: I agree with Dr Khanna completely. The brand-new hot-off-the-press IDSA guidelines do recommend fidaxomicin as our first-line treatment for initial C diff in severe and nonsevere cases. Using traditional dosing, we typically do twice a day for 10 days. But for recurrences, there are some great data with the extended-pulse dosing that you mentioned, where you essentially do a full dose twice a day for 5 days and then every other day for 20 days. The study that evaluated that regimen showed 1 of the lowest recurrence rates that we’ve ever seen in C diff studies. That’s a potential option for recurrence.
We mentioned oral vancomycin. Oral vancomycin used to be our go-to antibiotic for treating C diff,but it just wipes the gut microbiome. There are interesting studies show that when we take oral vancomycin, not only does it kill our gram-positive microbes, which it’s aimed to do, but because there’s such complex interplay among all our microbes in our gut, you can lose gram-negative bacteria as well. It’s interesting, which is why microbiome-sparing therapies like fidaxomicin can help to prevent future recurrences.
Dr Khanna, you mentioned cost. What’s underappreciated is just how much a recurrence can cost. We’re talking $10,000 to $12,000 to treat a patient who recurs in the hospital, and those initial drug acquisition costs with fidaxomicin can feel a little scary and give us some heartburn. But if you look at the cost-effectiveness, when looking through at least 1 or 2 recurrences, fidaxomicin is cost-effective in those settings.
James A. McKinnell, MD: Carl, how do you feel about that strategic approach for C diff?
Carl V. Crawford, MD: It’s important because if you step back and think about it, the treatment for C diff is the risk factor for its recurrence. One of those major phyla that we spoke about was Bacteroidetes. In particular, a specific group of bacteria, Bacteroidetes, are reduced by the presence of vancomycin. We were using this treatment to suppress C diff, but at the same time, we’re suppressing the colonization resistance. That’s what sets patients up for sometimes failure, because it’s a race against time as to what can reconstitute itself first after vancomycin has stopped.
Can C diff win out, or will the colonization resistance come back? It’s hit or miss. We don’t know who that’s going to happen for appropriately. We want our patients to do well, but we’ve just given them an antibiotic that hurts them. Using an agent that can spare the rest of the gram-negatives—Bacteroidetes like fidaxomicin—makes the most sense. It’s 1 of the reasons the IDSA decided to state that fidaxomicin should be preferred slightly over vancomycin. You can use either 1, but there’s that caveat that you should prefer to use fidaxomicin for this reason. It makes more sense biologically to use an agent that will spare your floor because the floor is so important in managing the pathophysiology of this particular infection.
James A. McKinnell, MD: Thank you for watching this Pharmacy Times® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box.
Transcript edited for clarity.