Treatment Options Differ in Initial, Recurrent C. difficile

October 2009

Metronidazole Is Recommended By So Many Textbooks And Guidelines That Its Use Can't Be Criticized

By Bruce Jancin
Elsevier Global Medical News

ESTES PARK, COLO. -- The treatment success rate for metronidazole in C. difficile-associated disease has definitely dropped off, compared with that of vancomycin, since the disease epidemiology changed around the year 2000, but the drug nevertheless retains a highly useful role for this infection.

That's because metronidazole's falloff in efficacy since the rise of community-acquired C. difficile-associated disease (CDAD) has been largely at the severe end of the disease spectrum, where vancomycin is now clearly the drug of choice.

In milder cases, metronidazole retains a respectable 90%-plus treatment success rate, Dr. Mary Bessesen said at a conference on internal medicine sponsored by the University of Colorado.

There are several good reasons to reserve vancomycin for the severe cases of CDAD. The emergence of vancomycin-resistant enterococci is a real concern, whereas metronidazole-resistant C. difficile has only rarely been seen. Plus, vancomycin is expensive. "In our pharmacy, vancomycin costs $18 per capsule," noted Dr. Bessesen, chief of infectious diseases at the Denver VA Medical Center.

Vancomycin remains the sole Food and Drug Administration-approved drug for CDAD, but metronidazole is recommended by so many textbooks and guidelines that its use can't be criticized, she continued.

The most common dose of vancomycin is 125 mg four times daily. The drug is safe for use in pregnancy and during breastfeeding. It's also well tolerated when given long term, an important consideration in recurrent CDAD. In contrast, the chronic use of metronidazole can result in neuropathy.

The natural history of CDAD is that 20% of patients will relapse after a first episode resolves. Retreatment with the same agent used in the initial episode will cure half of these first-time relapsers; the other half will have a second relapse. Subsequent relapses are harder to manage. Over 60% of patients who have a third relapse will subsequently have a fourth.

An oral vancomycin taper can be useful in managing multiple relapsers. It consists of 125 mg four times daily for 14 days, then 125 mg b.i.d. for 7 days, 125 mg once daily for 7 days, 125 mg once every other day for 8 days, and finally 125 mg once every 3 days for 15 days.

Two randomized clinical trials have demonstrated a 50% reduction in the CDAD recurrence rate with the use of the probiotic Saccharomyces boulardii. It is widely used in Europe, where it has regulatory approval, but it is not FDA approved. Because cases of invasive disease have been associated with the probiotic, Dr. Bessesen generally avoids the therapy in immunocompromised patients.

Antibiotic resistance is not the cause of recurrent CDAD. Currently, most patients are at home when they have a recurrence, so it's vital to minimize the risk of reinfection by instructing the family to decontaminate their home using a 10% bleach solution (1 cup of bleach in 1 gallon of water) to clean all hard surfaces.

Beyond metronidazole and vancomycin, the other available agents with activity against C. difficile have limited roles. Nitazoxanide is similar in efficacy to metronidazole and is an alternative in cases of metronidazole intolerance. Rifaximin is approved for treatment of traveler's diarrhea and has been used for recurrent CDAD; it's not recommended as initial therapy because resistance emerges in a single-step mutation. "My personal experience with rifaximin has been less favorable than reported in case series in the literature," Dr. Bessesen noted.

The use of tigecycline has been described in a handful of case reports. She views it as "an additional agent for desperate cases."


One promising investigational drug in the pipeline is OPT-80. It has minimal impact on normal gut flora and has shown good efficacy thus far in clinical trials.


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