ORIGINAL ARTICLE Rifaximin for the Treatment of Active Pouchitis: A Randomized, Double-blind, Placebo-controlled Pilot Study Kim L. Isaacs, MD, PhD,* Robert S. Sandler, MD, MPH,* Maria Abreu, MD, † Michael F. Picco, MD, ‡ Stephen B. Hanauer, MD, § Stephen J. Bickston, MD, P Daniel Present, MD, † Francis A. Farraye, MD, MSc, ¶ Douglas Wolf, MD,** and William J. Sandborn, MD, †† for the Crohn’s and Colitis Foundation of America Clinical Alliance Background: The efficacy of the nonabsorbable antibiotic rifaxi- min in patients with active acute or chronic pouchitis is unknown. Methods: We performed a placebo-controlled pilot trial to eval- uate the efficacy and safety of rifaximin in patients with active pouchitis. Eighteen patients with active pouchitis were randomized to receive oral rifaximin 400 mg or placebo 3 times daily for 4 weeks. Active pouchitis was defined as a total Pouchitis Disease Activity Index (PDAI) score = 7 points. Clinical remission was defined as a PDAI score 7 points and a decrease in the baseline PDAI score = 3 points. The primary analysis was clinical remission at week 4. Results: Eight patients were randomized to rifaximin and 10 patients were randomized to placebo. One patient in the placebo group did not have a post-baseline efficacy evaluation and was excluded from the efficacy analysis. Two of 8 patients (25%) treated with rifaximin were in clinical remission at week 4 compared to 0 of 9 patients (0%) treated with placebo (P = 0.2059). None of 8 patients in the rifaximin group withdrew from the trial prior to week 4. Two of 9 patients in the placebo group withdrew prior to week 4 due to lack of efficacy and were categorized as treatment failures. Conclusions: Clinical remission occurred more frequently in patients treated with rifaximin 400 mg 3 times daily but the differ- ence was not significant in this pilot study. A larger trial would be required to determine if rifaximin is effective for the treatment of active pouchitis. Rifaximin was well tolerated. (Inflamm Bowel Dis 2007;13:1250 –1255) Key Words: pouchitis, antibiotics, ulcerative colitis, inflammatory bowel disease P ouchitis is an idiopathic inflammatory disease of the ileal pouch that occurs in 15%–53% of patients who undergo total abdominal colectomy with ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC). 1–3 This condition is the most common complication of this proce- dure and is characterized by increased stool frequency with variable symptoms of urgency, rectal bleeding, inconti- nence, malaise, fever, and lower abdominal pain. 4 The etiology of pouchitis is not well understood but indirect evidence suggests a role for fecal bacteria. The goal of creating a pouch is to create a reservoir for stool that will allow continence. The end result of pouch formation is fecal stasis in the terminal ileum. Bacteriologic studies on the fecal contents of patients with pouches and patients with end ileostomies have demonstrated that patients with pouches have higher concentrations of stool anaerobes and Bacteroides as compared to patients with ileostomies. 5 Small randomized trials have suggested that antibiotic therapy with metronidazole and ciprofloxacin may be ef- fective for the treatment of active pouchitis. 6–8 However, metronidazole is poorly tolerated and treatment with sys- temically active antibiotics is not ideal from the perspec- tive of the development of antibiotic resistance. Rifaximin (Salix Pharmaceuticals, Morrisville, NC) is a poorly absorbed, non-aminoglycoside, semisynthetic antibi- otic derived from rifamycin O. 9 Rifaximin exerts its antibac- terial effect by binding to the beta-subunit of bacterial DNA- dependent RNA polymerase. The antimicrobial spectrum is broad and includes coverage for both aerobic and anaerobic Gram-positive and -negative organisms. Rifaximin is ap- proved to treat traveler’s diarrhea at a dose of 600 mg per day Received for publication April 19, 2007; accepted April 23, 2007. From the *University of North Carolina, Chapel Hill, North Carolina; † Mt. Sinai School of Medicine, New York, New York; ‡ Mayo Clinic Jacksonville, Jacksonville, Florida; § University of Chicago, Chicago, Illinois; P University of Virginia, Charlottesville, Virginia; ¶ Boston Medical Center, Boston, Mas- sachusetts; **Atlanta Gastroenterology Associates, Atlanta, GA; †† Mayo Clinic, Rochester, Minnesota. Supported by research grants from Salix Pharmaceuticals, Morrisville, NC, and the Crohn’s and Colitis Foundation of America, New York, NY. Maria Abreu, Stephen Hanauer, Kim Isaacs, Daniel Present, and William Sandborn have served as consultants for Salix. Maria Abreu, Stephen Hanauer, Stephen Bickston, Francis A. Farraye, and Daniel Present have participated in Continuing Medical Education events or Speakers Bureau Events indirectly or directly sponsored by Salix. Reprints: Kim L. Isaacs, MD PhD, University of North Carolina at Chapel Hill, Division of Gastroenterology and Hepatology, CB# 7032, Room 7200 MBRB, Chapel Hill, NC 27599-7032 (e-mail: klisaacs@med.unc.edu). Copyright © 2007 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20187 Published online 13 June 2007 in Wiley InterScience (www.interscience. wiley.com). 1250 Inflamm Bowel Dis ● Volume 13, Number 10, October 2007