Vancomycin’s Benefits in C. difficile Declining

Metronidazole and vancomycin have been the mainstays of therapy for Clostridium difficile–associated disease (CDAD) for 25 years. Metronidazole often is chosen as the initial treatment because it costs less and using it reduces selection pressure for the emergence of vancomycin-resistant enterococci. Vancomycin, however, reaches much-higher concentrations in the stool than does metronidazole and often is considered the more effective agent; it is particularly useful as first-line therapy for patients with severe CDAD and in cases in which metronidazole has failed or cannot be used.

Beginning in 2000, hospitals in the U.S. and Canada, and later in Europe, reported outbreaks of severe disease associated with a hypervirulent strain of C. difficile (NAP1/027). Now, researchers have conducted a retrospective cohort analysis to assess the comparative effectiveness of vancomycin and metronidazole before the emergence of NAP1/027 (1991–2002) and during the epidemic period (2003–2006). They examined records for 1616 patients who were treated for CDAD at a tertiary care hospital in Quebec between January 1991 and August 2006. The patients were treated initially with vancomycin (219), metronidazole (1360), or both (37); all were followed for 60 days after diagnosis. Severe or complicated CDAD was defined as death within 30 days of diagnosis, septic shock, megacolon, perforation, or need for emergency colectomy.

During both study periods, the significant risk factors for severe or complicated CDAD were immunosuppression, marked leukocytosis, and elevated creatinine levels. Compared with initial metronidazole therapy, initial vancomycin treatment was associated with a lower risk for severe or complicated CDAD from 1991 to 2002 but not from 2003 to 2006. After adjusting for the identified risk factors, the authors found that the emergence of NAP1/027 accounted for the loss of vancomycin’s superiority over metronidazole.