TORONTO — Vancomycin is a better first-line treatment for severe cases of diarrhea caused by Clostridium difficile infection than metronidazole, Dr. Melinda B. Davis said at the annual meeting of the Infectious Diseases Society of America.
In a prospective, placebo-controlled trial designed to compare the efficacy of vancomycin and metronidazole (Flagyl) for the treatment of C. difficile-associated diarrhea, 172 patients who tested positive for the C. difficile toxin A or B in the stool and had three or more loose stools per day or who had pseudomembranous colitis on endoscopy were randomized to receive 125 mg of liquid vancomycin and a placebo tablet or a 250-mg tablet of metronidazole and a placebo liquid for 10 days.
After randomization, 22 patients were withdrawn from the study because of noncompliance, intolerance, loss to follow-up, or death before day 3 of therapy. Of the remaining 150 patients, 71 were in the vancomycin group and 79 were in the metronidazole group.
Patients were categorized with severe C. difficile-associated diarrhea if they had endoscopy-proven pseudomembranous colitis, if they required treatment in the intensive care unit, or if they had two of the following: fever, elevated white blood cell count, low albumin, or age older than 60 years. Diarrheal disease that did not meet these criteria was classified as mild.
The cure rate in the 31 patients with severe diarrhea in the vancomycin group was 97%, compared with 76% for the 38 patients with severe diarrhea in the metronidazole group, said Dr. Davis of the University of Illinois at Chicago. In those with mild diarrhea, including 40 patients on vancomycin and 41 on metronidazole, cure rates were similar, 98% and 90%, respectively. Patients were considered cured if the diarrhea resolved within 6 days of treatment initiation and if the resolution was sustained through day 10.
In severe and mild disease, relapse rates were higher among patients treated with metronidazole compared with those treated with vancomycin. The rate of disease recurrence within 21 days of successful treatment completion in those with severe disease was 10% in the vancomycin group and 21% in the metronidazole group. For those with mild disease, 5% of those on vancomycin and 8% of those on metronidazole relapsed.
Dr. Davis reported no financial disclosures with respect to her presentation.