JAC Advance Access originally published online on March 2, 2007
Journal of Antimicrobial Chemotherapy 2007 59(4):705-710; doi:10.1093/jac/dkl553
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Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide
1 Medical Service (Infectious Disease Section), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA 2 Departments of Medicine and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA
Received 3 November 2006; returned 6 December 2006; revised 20 December 2006; accepted 21 December 2006
* Correspondence address. Infectious Disease Section, Veterans Affairs Medical Center, 2002 Holcombe Boulevard, Houston, TX 77030, USA. Tel: +1-713-794-7386; Fax: +1-713-794-7045; E-mail: daniel.musher{at}med.va.gov
Objectives: Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic-resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole.
Methods: In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after 
14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included.
Results: Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%).
Conclusions: Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole.
Keywords: antibiotic-associated diarrhoea , vancomycin , C. difficile
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