Treatment Options Differ in Initial, Recurrent C. difficile
ESTES PARK, COLO. — The treatment success rate for metronidazole in C. difficile–associated disease has dropped off, compared with that of vancomycin, since the disease epidemiology changed around the year 2000, but the drug retains a highly useful role for this infection.
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 the drug of choice. In milder cases, metronidazole retains a respectable 90%-plus success rate, Dr. Mary Bessesen said at a conference on internal medicine sponsored by the University of Colorado.
Keeping vancomycin in reserve for severe cases of CDAD makes sense because the emergence of vancomycin-resistant enterococci is a real concern, whereas metronidazole-resistant C. difficile remains rare. 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, 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 first-time relapsers; the other half will have a second relapse. Subsequent relapses are more difficult to manage. More than 60% of patients who have a third relapse will later 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 shown 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. Cases of invasive disease have been associated with the probiotic, so Dr. Bessesen generally avoids the therapy in immunocompromised patients.
Antibiotic resistance is not the cause of recurrent CDAD. 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.
Other 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 treating 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. Tigecycline, described in a few case reports, is “an additional agent for desperate cases,” she said.
Metronidazole is recommended by so many textbooks and guidelines that its use can't be criticized.
Source DR. BESSESEN
