Nitazoxanide for the Empiric Treatment of Persistent Diarrhea

Abstract

Purpose: Persistent diarrhea is a common complaint of patients presenting to family practitioners, internists, and gastroenterologists. The differential diagnosis is complex, and the variety of tests applicable to these patients can be overwhelming. Accurate diagnosis is elusive, as there are multiple potential etiologies of persistent diarrhea, many of which are infectious in origin. A successful trial with an antibiotic for treatment of enteric pathogens would potentially eliminate the need for a more extensive evaluation. Nitazoxanide (NTZ) is a first in class thiazolide antibiotic with activity against anaerobic bacteria, protozoa, helminthes, and gastrointestinal viruses. This unique spectrum makes nitazoxanide active against the most common infectious etiologies of persistent diarrhea. Furthermore, NTZ has a placebo-like safety profile, and concentrates in the GI tract. The purpose of this review is to report clinical experience using NTZ as empiric therapy for the treatment of persistent diarrhea. Methods: A multi-center chart review was performed on patients treated with NTZ from April 2006 to April 2008 with complaints of persistent diarrhea (>14 days) of unknown etiology. Patients were excluded if they had a known infectious cause of diarrhea such as Clostridium difficile or bacterial overgrowth. Efficacy was measured as patient reported complete resolution of diarrhea or satisfactory improvement of symptoms by the end of therapy. Follow-up evaluations were made either via office visits, or telephone interview. Nineteen patients met the inclusion criteria for review. Results: Of the 19 patients treated with NTZ, 14 were available for follow-up. Diarrhea was considered to be persistent in 13 of 14 patients, and one patient was excluded due to a positive lactulose breath test prior to treatment. This left a total of 12 patients for the final analysis. The range of NTZ used was 500 mg BID-TID from 3–10 days, with the median dose and duration of therapy being 1000 mg/day × 7 days. Overall, 10/12 (83%) of the patients studied had a resolution of diarrhea, with 6 of the patients having a complete response, and 4 of the patients having satisfactory improvement. Of the two non-responders, one patient was later diagnosed with microscopic colitis which responded to prednisone, and the other was determined to have diarrhea secondary to radiation therapy. One patient who complained of GI distress while on NTZ had to discontinue therapy, but still had a complete response. Otherwise, NTZ was well-tolerated. Conclusion: Nitazoxanide appears to be a safe and effective alternative for the empiric treatment of persistent diarrhea. More studies are necessary to confirm these results.