Initiating Therapy in Newly Diagnosed <i>C Difficile</i>

Peter Salgo, MD: I want to talk about treatment. We’ve established the diagnosis. Now, we’re going to deal with this. It’s nontrivial, in my experience, anyway. When you go to initiate therapy in a newly diagnosed patient with Clostridium difficile [C. diff], can you divide patients into groups? How do you start? How do you make decisions?

Dale N. Gerding, MD: The previous guidelines definitely were focused on the severity of the C. diff diarrhea, whether your creatinine was 1.5 times higher than your baseline, or if your white blood cell count was 15,000 or more. The new guideline really doesn’t differentiate as much on the basis of severity. Instead, in the recommendation, the big change is that metronidazole, which had kind of been a workhorse treatment drug for the past 20 years, is no longer recommended as first-line therapy.

Peter Salgo, MD: In either case?

Dale N. Gerding, MD: In either case. If a patient has nonsevere disease, the recommended therapy is now either vancomycin or fidaxomicin. But, if you have difficulty accessing those drugs, which are more expensive—the guideline says “accessing,” which is code for, “I can’t afford vancomycin or fidaxomicin,” or, “I can’t get it approved by my insurance company,” or for whatever the reason may be&mdash;then metronidazole could be used. It can only be used for these nonsevere cases. It can’t be used for severe cases.

Peter Salgo, MD: Why is metronidazole out? Is it less effective? Does it not work? What’s the problem?

Dale N. Gerding, MD: We finally got a good prospective large blinded trial of metronidazole versus vancomycin, and it finally showed that metronidazole is inferior to vancomycin, across the board, for all patients. That was a convincing piece of data. In 1983, we did one of the first trials on metronidazole. We couldn’t see any difference between metronidazole and vancomycin. But, that trial was not large enough. We mistakenly said that these drugs were equivalent. We should never have said that. It was a big mistake. Now, we have enough data. And metronidazole, by the way, never went through FDA approval as a treatment.

Peter Salgo, MD: It was off-label.

Dale N. Gerding, MD: It was already a generic drug by the time it was tried, so it never went through the process.

Peter Salgo, MD: So, you’re telling me that you did something almost unheard of—you got good data?

Dale N. Gerding, MD: Exactly.

Peter Salgo, MD: And good data convinced you that metronidazole was not the way to go?

Dale N. Gerding, MD: Exactly.

Peter Salgo, MD: That’s pretty straightforward.

Yoav Golan, MD: Metronidazole doesn’t make much sense for C. diff because it’s a systemic antibiotic. C. diff all happens in the gut. But, it may also be that some of the strains we’ve seen emerging are less treatable with metronidazole. They cause more severe disease, they’re less susceptible, and so forth. If there is any resistance to any antibiotic—which is reported, but not very often&mdash;it is to metronidazole, far more often.

Peter Salgo, MD: Let me turn this back around. Maybe you were just fine with metronidazole, at first. But, the landscape has changed. The bacteriology has changed. Now, we’re seeing ones that are less sensitive to metronidazole than they were.

Dale N. Gerding, MD: The first part is correct, but the last part is not. The new strains, we think, are not as likely to respond to metronidazole as the previous strains. I don’t think you can blame it on resistance to the drug. It’s something else. We don’t know what it is, but, clearly, metronidazole is not working as well as it did for the previous 15 or 20 years, prior to year 2000. So, I think the strains are different, and it clearly is a changing landscape.

Darrell S. Pardi, MD: I’d like to make a distinction between microbiologic resistance and clinical resistance. There’s not much evidence of microbiologic resistance in the petri dish. But, in the patient, there’s multiple studies—a randomized controlled trial and multiple observational studies&mdash;showing that up to 30%, 35% of patients don’t respond to metronidazole. So, clinically there is resistance.

Transcript edited for clarity.