Nitazoxanide to Treat Community Acquired Clostridium difficile-Associated Disease

Abstract

Purpose:Clostridium difficile-associated disease (CDAD) is a significant problem which is increasing in incidence and severity in hospitalized patients. Concern has started to focus on outpatients as well with community acquired (CA)-CDAD. The ACG treatment guidelines for CDAD (AJG 1997;92:739–50) recommend metronidazole (MTZ) as initial therapy for most patients with CDAD, however recent studies document failure rates up to 50% with MTZ (CID 2005;40:1586–90, CID 2006;43:421–7). In the past, the only other antibiotic available to clinicians was vancomycin (VAN), the only FDA indicated antibiotic for CDAD. VAN remains a very effective agent for CDAD, but concerns of cost, frequent dosing (QID), and the potential to promote VAN resistant Enterococcus has left clinicians to look for different therapies. A new thiazolide antibiotic, nitazoxanide (NTZ), has demonstrated efficacy for CDAD in trials versus MTZ and VAN, as well as in patients who have failed MTZ (JAC 2007;59:705–10, DDW 2008: Presentation W1272). Like VAN, NTZ is highly active against CD, concentrates in the GI tract and has no known in vitro resistance. The purpose of this study is to evaluate the effectiveness of NTZ in patients with CA-CDAD. Methods: Outpatients reporting to the clinic with diarrhea and clinical features consistent with CDAD and a positive stool test for CD toxins A or B (Diagnos-Techs, Inc., Kent, WA) were eligible for evaluation. CA-CDAD was defined as eligible patients with no known previous hospitalizations 3 months prior to presentation. All patients were treated with NTZ 1000 mg BID for 14 days and encouraged to take a probiotic. Follow-up evaluations including a repeat stool toxin test was made 1–4 weeks after the cessation of therapy to assess clinical efficacy. Results: Overall, 58 patients met the inclusion criteria, 22 males, 36 females, mean age 44 years (range 8–77). At the follow-up evaluation (mean 10 days, range 7–30) 53 (91%) patients were considered a clinical cure. Of the five treatment failures, four patients and their significant others (SO) were retested for CD stool toxins. In all four cases the SO also had a positive stool toxin assay. These patients and their SO were retreated with a second course of NTZ 1000 mg BID for 14 days. Upon retreatment each patient and SO was considered a clinical cure. No clinically significant adverse reactions to NTZ were identified. Conclusion: NTZ is a safe and effective treatment for CA-CDAD. Clinicians should consider testing significant others as a potential CD carrier when patients fail therapy. Further epidemiologic evaluations and clinical studies with NTZ are needed to determine the incidence and severity of CA-CDAD, the relevance of significant contacts, and the efficacy of NTZ in this population.