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Is Metronidazole the Standard for C. difficile–Associated Disease?

For treatment of Clostridium difficile–associated disease, neither metronidazole nor vancomycin emerges as a clear winner.

Clostridium difficile–associated disease (CDAD) has become a major nosocomial infection. Metronidazole is the preferred treatment, in part because of concerns about inducing vancomycin resistance in other pathogens. However, two reports raise concern that metronidazole may not be as effective as previously thought.

Musher and colleagues conducted a prospective observational study of patients with CDAD treated at a Houston medical center where the use of oral vancomycin was restricted. All received metronidazole (1.5 g/day) for 7 days. Among 207 patients, 50% had a complete cure without relapse, 22% continued to have symptoms or signs of colitis for 10 days, and 28% responded initially but experienced a recurrence of CDAD within 90 days after completing therapy. Neither metronidazole resistance nor a C. difficile epidemic clone accounted for the comparatively poor response to therapy.

A group headed by Pépin (who has received funding from a vancomycin manufacturer) retrospectively reviewed data on CDAD recurrence at a large Quebec hospital from January 1991 through June 2004. The percentage of patients switched from metronidazole to vancomycin because of poor response increased from 10% through 2002 to 26% during 2003–2004 (P<0.001). Among those treated with metronidazole, the incidence of recurrence increased from 21% through 2002 to 47% during 2003–2004 (P<0.001). Recurrences were particularly high among those 65 years old.

Comment: Both studies were observational. In neither can one conclude that metronidazole was inferior to oral vancomycin for CDAD, because no comparison was made. What they both indicate is that CDAD is a worsening problem in our hospitals. The explanation probably is multifactorial. Elderly patients represent an increasing proportion of hospitalized patients, and older age has been associated with diminished immune response to C. difficile. Moreover, evidence exists that a new strain of C. difficile is becoming epidemic in North American hospitals. Controlled studies of various new treatment agents, already under way, should better define the best therapy for CDAD in the 21st century.

— Neil M. Ampel, MD

Published in Journal Watch Infectious Diseases July 8, 2005

Citation(s):

Musher DM et al. Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis 2005 Jun 1; 40:1586-90.

• Medline abstract (Free)

Pépin J et al. Increasing risk of relapse after treatment of Clostridium difficile colitis in Quebec, Canada. Clin Infect Dis 2005 Jun 1; 40:1591-7.

• Medline abstract (Free)