University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• Is nitazoxanide more effective than metronidazole in treating hospitalized patients with C. difficile colitis?

Clinical Bottom Lines

1. Nitazoxanide is as effective as Metronidazole for treatment of C. difficile colitis.
2. There was a trend towards greater rate of response in the group treated with nitazoxinide, but the sample size was too small to demonstrate a difference.

Summary of Key Evidence

1. Prospective, randomized double blind multicenter trial
2. Adult inpatients from 7 medical centers, with diarrhea (more than 3 liquid stools within 24h), positive EIA for CD, fever abdominal pain or leucocytosis
3. Patients with other causes of diarrhea, clinically instable, with allergy to metronidazole were excluded
4. Patients were randomized to 3 treatment groups: 1) metronidazole 250g q 6h; 2) nitazoxinide 500mg q12h for 7 days and 3) nitazoxinide 500mg q12h for 10 days
5. Followup on days 8, 11-14 and 31
6. Detection of CD by EIA
7. Primary endpoint : clinical response after 7 days of treatment. Secondary endpoints: Rate of response to nitazoxinide at day 7 was determined and compared with metronidazole. Sustained response was evaluated at day 31.
8. 95% confidence interval was calculated for the difference between response rates. Resolution of symptoms between groups was compared using Kaplan-Meyer survival analysis. Rate of adverse effects was compared using χ2 or Fisher’s exact test.
9. Groups had similar demographics and similar disease severity. There was no significant difference between groups in the to resolution of symptoms, clinical response at 7 days and sustained response at 31 days.
10. The rate of adverse effects was similar in the 3 groups and reflects the severity of underlying disease in all three groups.

Additional Comments

• Metronidazole is the first line treatment for C. difficile colitis. However, treatment failure and recurrence of infection with metronidazole is increasing.
  • Nitazoxanide has been used successfully to treat intestinal infestations. In vitro nitazoxanide, and its breakdown product tizoxanide, inhibit C. difficile.
  • After oral administration 2/3 of nitazoxinide is excreted in the feces.

Citation

CAT Author: Vera De Matos, MD

CAT Appraisers: Francis McBee Orzulak, MD

Date appraised: 10/22/2008