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Severe Clostridium difficile colitis may produce abdominal distention and ileus, precluding oral antibiotic therapy. Stimulated by several case reports in which intravenous metronidazole was used, we reviewed our experience.Using pharmacy and microbiology laboratory records, we retrospectively identified patients with C. difficile colitis who received intravenous metronidazole as initial monotherapy. To be included, patients had to fulfill the following criteria: 1) at least six doses (equivalent to two days of therapy) of intravenous metronidazole were administered, 2) no other potential cause for colitis was found, and 3) the diagnosis of C. difficile colitis was firmly established. For eligible patients, five clinical parameters were assessed before and after intravenous metronidazole.Our patient group (n=10) received an average of 13.7 (range, 6-24) doses of intravenous metronidazole as initial therapy for C. difficile colitis. All received a dose of 500 mg three times daily. The majority of patients with vomiting, fever, and/or abdominal pain present at the beginning of therapy had resolution with intravenous metronidazole. Only one patient developed a symptom (vomiting) while on therapy; however, this eventually resolved when oral metronidazole was instituted. No patient required colectomy for refractory colitis or developed toxic megacolon. No patient, including those on prolonged courses, developed toxicity related to intravenous metronidazole such as peripheral neuropathy.Intravenous metronidazole may be effective therapy in patients with C. difficile colitis. A randomized, prospective study appears warranted.