Treatment Options Differ in Initial, Recurrent C. difficile
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
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
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
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