In recent years, reports have emerged describing the failure of metronidazole as therapy for Clostridium difficile–associated disease (CDAD). Although the microbiological basis for metronidazole failure in CDAD is unknown, levels of metronidazole in the gastrointestinal tract are much lower than those of vancomycin. Now, in a prospective, observational study partially funded by vancomycin’s manufacturer, researchers in Cleveland have compared the use of these drugs in 52 patients who were diagnosed with CDAD between November 2006 and July 2007.
Of the 34 patients initially treated with metronidazole, 10 (29%) were switched to vancomycin after 3 to 10 days because their symptoms persisted. None of the 18 patients initially treated with vancomycin were switched, although 1 had nitazoxanide added to his regimen. After adjustment for confounding factors, patients initially treated with vancomycin were significantly more likely than those initially given metronidazole to have resolution of diarrhea (P=0.005) and to achieve undetectable levels of C. difficile in the stool (P=0.009) during the first 5 days of therapy. Isolates from the 10 patients who were switched from metronidazole to vancomycin were all susceptible to metronidazole (MIC
0.75 µg/mL). However, these patients showed no significant decrease in C. difficile concentrations during metronidazole therapy.Comment: The observational nature of this study is problematic. Nonetheless, the findings suggest that metronidazole is less effective than vancomycin in reducing fecal concentrations of C. difficile early in the course of treatment. Low levels of metronidazole in the gut, rather than resistance, may have been the cause for some patients’ suboptimal response to the drug.
— Neil M. Ampel, MD
Published in Journal Watch Infectious Diseases June 25, 2008