An ongoing dialogue on HIV/AIDS, infectious diseases,
March 31st, 2010
C diff Guidelines: Metronidazole Still Preferred?
IDSA and The Society for Healthcare Epidemiology of America (SHEA) have published Clinical Practice Guidelines for Clostridium difficile infection.
Not surprisingly, it’s a comprehensive, extensively-referenced document that will be an invaluable resource, especially since the previous version is approximately 15 years old.
But with the caveat that I’m not an expert in this area, these particular treatment recommendations continue to perplex me:
Metronidazole is the drug of choice for the initial episode of mild‐to‐moderate Clostridium difficile infection (CDI). The dosage is 500 mg orally 3 times per day for 10–14 days.
Vancomycin is the drug of choice for an initial episode of severe CDI. The dosage is 125 mg orally 4 times per day for 10–14 days.
In what other diseases do we recommend something different for mild vs. severe infection, when both are oral options? I understand there is a cost difference, but since the data on treatment of severe CDI demonstrate the superiority of vancomycin, is this the right approach? Especially since oral vancomycin is better tolerated?
Or are we still going through this widely-quoted (and frankly kind of politically incorrect!) mom vs mother-in-law dilemma?
With the intention of being provocative, what would you take if you had C diff?
6 Responses to “C diff Guidelines: Metronidazole Still Preferred?”
Paul E. Sax, MD
Contributing Editor
NEJM Journal Watch
Infectious Diseases
Biography | Disclosures | Summaries
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I try to be one of those compliant docs that follow the guidelines, but vanc is better tolerated and we know it is superior to metronidazole in the sickest patients. The other part of the guideline I struggle with is the dictum to re-treat patients with the same drug when they present with a recurrence. Even though we know that most cases of recurrence are due to re-infection and not resistence, I have found this to be a tough sell to patients (…you mean you are giving me the SAME drug I just failed???…OK, I GUESS you know what you are doing…)
One of the reasons metronidazole was preferred historically, in addition to cost and the small, older studies showing equivalence, was that it didn’t promote vancomycin-resistant enterococcal infection, in an era when there was no effective therapy for VRE. There was also a lurking fear that promiscuous vancomycin use would eventually lead to emergence of vancomycin-resistant Staph aureus. So the metronidazole vs. vancomycin debate is similar to the ethical quandary of the prisoner’s dilemma: what is best for the individual is not necessarily best for society at large. For the record, if it were me, I’d prefer vancomycin!
Yep, I remember that rationale — but I don’t think it’s been borne out in actual studies, possibly because metronidazole tremendously alters “normal” GI flora by wiping out all those anaerobes (and thereby potentially promoting VRE).
Why would anyone want to take something less effective and more difficult to tolerate (metronidazole) and wait to see what happens? Additionally, what validated symptom scale are we to use to separate mild from severe C. Diff? To the patient who is miserable, everything is severe! This recommendation (to treat patients with C. diff differently) may seem scientific, but it is irrational and irrelevant when delivering care to a single specific patient with C. diff.
Oral vancomycin capsules remain incredibly expensive, which can be cost-prohibitive for patients lacking adequate prescription insurance. Oral metronidazole is substantially less expensive and the notion that it is less effective is based on questionable observational studies, so using it first line for mild CDI is not all that unreasonable. With that being said, it’s understandable that we always strive to provide the best possible therapies for our patients, sometimes finical barriers abound. A substantially less expensive option for patients requiring oral vancomycin is compounding an oral vancomycin solution from the IV formulation. We have been using that for our hospitalized patients for several years now and aside from the unpleasant taste it works extremely well and costs a fraction of the price of the capsules. We have even prescribed this formulation for outpatients who otherwise would not have been able to afford therapy. This option is also noted in the new SHEA guideline as well…
Yes, Vancomycin is superior to Metronidazole when used in treating Clostridium Difficille Infection (CDI)but its prohibitive cost makes Metronidazole a prefferable drug for use in developing countries like Tanzania.
Metronidazole is cheap and seem not to provoke resistance.