title: Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.
abstract: OBJECTIVE
  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 >or= 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.
authors.affiliation: Medical Service (Infectious Disease Section), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, USA. daniel.musher@med.va.gov
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Musher
authors.forename: Nancy
authors.initials: N
authors.lastname: Logan
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Mehendiratta
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Melgarejo
authors.forename: Sagar
authors.initials: S
authors.lastname: Garud
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hamill
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016360:Clostridioides difficile; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D009574:Nitro Compounds; D012008:Recurrence; D013844:Thiazoles / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D009574:Nitro Compounds; D013844:Thiazoles; D008795:Metronidazole; C041747:nitazoxanide