Four-week open-label trial of metronidazole and ciprofloxacin for the treatment of recurrent or refractory pouchitis

Background: Preliminary data suggest that short-term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis. However, some patients are resistant to treatment. Aim: To evaluate the therapeutic efficacy of a prolonged course of a combination of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life. Methods: Patients with active refractory or recurrent pouchitis were recruited. This was defined as both: (I) a history of pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis Disease Activity Index score (3) 7 (best to worst pouchitis = 0-18) at the beginning of therapy. Treatment consisted of a combination of metronidazole, 400 or 500 mg, twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days. Symptomatic, endoscopic and histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of less than or equal to 2, endoscopic score of less than or equal to 1 and total score of less than or equal to 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire, which encompasses bowel, systemic and emotional symptoms as well as social function (worst to best = 32-224). Results: Forty-four patients (24 male, 20 female; median age, 37.5 years) entered the trial and completed treatment. Thirty-six (82%) went into remission. The median Pouchitis Disease Activity Index scores before and after therapy were 12 (range, 8-17) and 3 (range, 1-10), respectively (P < 0.0001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 96.5 (range, 74-183) to 175 (range, 76-215) with this therapy (P < 0.0001). The eight patients (five male, three female) who did not go into remission were significantly older (median 47.5 vs. 3 5 years; P = 0.007), had a longer history of pouchitis (95.5 vs. 26 months; P = 0.0008), had a greater proportion with chronic pouchitis (chronic/relapsing: 6/2 vs. 9/27; relative risk, 1.6; 95% confidence interval, 1.0-2.4) and tended to have a higher Pouchitis Disease Activity Index score before treatment (median 14.5 vs. 12; P = 0.13) than those who went into remission. Even in these eight patients, the median Pouchitis Disease Activity Index score significantly improved from 14.5 (range, 8-16) to 9.5 (range, 7-10) (P = 0,007/8), as did the Inflammatory Bowel Disease Questionnaire score from 95.5 (range, 74-134) to 127 (range, 76-187) (P = 0.039). The Inflammatory Bowel Disease Questionnaire score strongly correlated with the Pouchitis Disease Activity Index score (r = 0.79, P < 0.0001), and was significantly related to the patients' overall assessment of satisfaction (P < 0.0001). No serious side-effects were noted. Conclusions: Four-week treatment with a combination of metronidazole and ciprofloxacin is highly effective in patients with active recurrent or refractory pouchitis, objectively improving the inflammation and quality of life. The Inflammatory Bowel Disease Questionnaire is a sensitive tool for evaluating patients with pouchitis, and correlates well with disease activity.