Treatment Options for Newly Diagnosed <i>C Difficile</i>

Peter Salgo, MD: You brought up fidaxomicin. That’s a very new drug. How does it work? What is it active against? How does it affect the microbiota completely?

Dale N. Gerding, MD: Fidaxomicin was approved by the FDA after the previous guideline had already been published, so it wasn’t even in the previous guideline. Fidaxomicin did undergo phase 3 comparative trials against vancomycin. It cured Clostridium difficile (C. diff) equally as well as vancomycin did, but it significantly reduced recurrent C. diff—dropping the recurrence rate from around 25% down to around 15% or 14%.

Peter Salgo, MD: That’s a big drop.

Dale N. Gerding, MD: It’s very significant. Right now, I think it is probably the best drug that we have for C. diff, in terms of both cure and reduced recurrence.

Peter Salgo, MD: It’s gone through better FDA review, if you will, against C. diff than other drugs had in the past—they didn’t go through any review at all.

Dale N. Gerding, MD: Vancomycin has been tested and did have FDA approval, but metronidazole never went through the trials.

Peter Salgo, MD: What about the other microbiota? Do we know what it’s doing?

Dale N. Gerding, MD: The reason why fidaxomicin has a lower recurrence rate is that it is not as damaging to the microbiome as vancomycin is. That’s been shown repeatedly. Although we don’t know for sure what the mechanism is, that is the one that everybody thinks is most likely to reduce recurrence.

Peter Salgo, MD: We have this new drug, fidaxomicin. We have the old standard, which was reviewed by the FDA—vancomycin. To us, we’ve got a new case of C. diff. How do you go about deciding between vancomycin and fidaxomicin? Is there a huge price difference?

Yoav Golan, MD: There is a price difference. Fidaxomicin is a branded antibiotic, so it’s far more costly to acquire when you talk about the acquisition price. When you talk about price, in general, I think you have to take into account the price of having a recurrence of C. diff and the cost to care for it if you have an antibiotic. It’s important to realize that in the study, compared with vancomycin, fidaxomicin was considered to be superior by the FDA in terms of sustained response—so having a cure and not having a recurrence. We actually have put together an algorithm, or a clinical pathway, to guide our clinicians in the hospital on how to choose between vancomycin and fidaxomicin. We use fidaxomicin for any patient whom we consider to be at high risk for recurrent C. diff. Now, this could be a completely different, additional discussion—who is at high risk?

Peter Salgo, MD: I was just going to go there. If you’re going to make that your decision point, how do you decide who’s going to be at risk for recurrent C. diff?

Yoav Golan, MD: So in our pathway, once someone has tested positive for C. diff, if we think they have C. diff and they have unexplained diarrhea, we have to make the choice between vancomycin and fidaxomicin. Unlike in the past, we rarely now treat patients empirically unless we are completely convinced that they have C. diff from the get-go—as you said, this patient all of a sudden developed explosive diarrhea and a huge leukocytosis, which is usually not the most typical presentation of C. diff, or the patient is very sick. We actually avoid using empiric therapy, which I think is very important because 90% of the C. diff tests actually end up being negative.

And so when the test result comes back, that’s when we make the treatment decision. We go with fidaxomicin in any patient whom we consider to be at high risk. We mainly look at 3 risk factors. One is the age of the patient. There is a relationship between risk of recurrence and age. Results from studies that we have done have shown that recurrence is usually very uncommon in patients below the age of 40. Above the age of 40, increasing recurrence is kind of linear. So it’s very artificial—where you put your age point. Many people would use age 65 or older as the age point. We actually use age 70 in our current algorithm. We go by history of C. diff. So anyone who had C. diff in the past is clearly at high risk for redeveloping C. diff. We also go by an emerging risk factor, which is kidney dysfunction. We go by estimated creatinine clearance. If their estimated creatinine clearance is less than 65 in our hospital, we consider them to be at high risk for recurrence. As a result, we probably treat 25% or 30% of our patients with fidaxomicin. In the rest, we give vancomycin.

Peter Salgo, MD: Twenty-five or 30% is less than I thought you were going to tell me. That’s not most of the patients.

Yoav Golan, MD: You’re right. If one antibiotic is superior to another, why would you use the other at all? There are several reasons for that. Obviously, the main reason is the cost. Sometimes, the patient has some costs in addition to the cost to the care system—the cost to the hospital. As you know, hospitals do not get reimbursed for medications that they use during hospitalization. And so the cost has been the main reason to not use fidaxomicin in everyone. If the cost were equivalent for vancomycin and fidaxomicin, fidaxomicin would probably be the first drug to be used because it’s clearly superior to vancomycin. But again, as I mentioned earlier, I think that when you look at the cost, even as a hospital, you have to look at the cost of recurrence. You have to look at those patients being readmitted to the hospital within a month, and that may be a very large cost as well.

Peter Salgo, MD: You wanted to say something?

Darrell S. Pardi, MD: Yes. This gets back to what Yoav said earlier, about acquisition cost. If you have a patient in the hospital, the acquisition cost for the drug goes to the hospital pharmacy. At my institution, there was a big review of fidaxomicin. It is the best drug we currently have available for C. diff. If cost wasn’t an issue, it would be the first drug that we would use. That’s not the real world. The pharmacy, at my institution, estimated that it would break their budget if we used fidaxomicin, first line, for hospitalized patients with C. diff. So we do the same thing that Yoav does—we try to risk-stratify. It’s an imperfect algorithm, but we try to select the patients who are at highest risk for recurrence, who should achieve the biggest benefit.

Transcript edited for clarity.