1 Literature Review Peter R. McNally, DO, FACP, FACG University of Colorado School of Medicine Center for Human Simulation Aurora, Colorado 80045

2 Scarpellini E, Gabrielli M, Lauritano C, Lupascu A, Merra G, Cammarota G, Cazzato IA, Gasbarrini G, Gasbarrini A. High Dose Rifaximin for Treatment of Small Intestinal Bacterial Overgrowth. Alimentary Pharmacology & Therapeutics. 2007;25: Valencia, Spain

3 Introduction Small intestinal bacterial overgrowth (SIBO) is a burgeoning field of study in the etiology of Irritable Bowel Syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) is a burgeoning field of study in the etiology of Irritable Bowel Syndrome (IBS). Many antibiotics have been examined in the treatment of SIBO. (Lin HC. JAMA 2004;292: ) Many antibiotics have been examined in the treatment of SIBO. (Lin HC. JAMA 2004;292: ) – Metrinodizole – Ciprofloxacin – Tetracycline – Neomycin – Rifaximin Rifaximin is a non absorbed, intra-luminal antibiotic that appears to have the best efficacy in treatment of this disorder. Rifaximin is a non absorbed, intra-luminal antibiotic that appears to have the best efficacy in treatment of this disorder. Scarpellini E, et al. Aliment Pharm Ther. 2007;25:

4 Aim Scarpellini et al, conducted a dose ranging trial of Rifaximin at doses of 1600 mg/day vs mg/day to assess efficacy, safety and tolerability in the treatment of SIBO. Scarpellini et al, conducted a dose ranging trial of Rifaximin at doses of 1600 mg/day vs mg/day to assess efficacy, safety and tolerability in the treatment of SIBO. Scarpellini E, et al. Aliment Pharm Ther. 2007;25:

5 Study Design: 80 consecutive pts with SIBO were enrolled. 80 consecutive pts with SIBO were enrolled. Diagnosis of SIBO based upon clinical history and positive Glucose Breath Test (GBT), defined as > 20 ppm rise in H 2 /CH 4. Diagnosis of SIBO based upon clinical history and positive Glucose Breath Test (GBT), defined as > 20 ppm rise in H 2 /CH 4. Treatment randomized to 7- days of Rifaximin 1600 mg/d (Group 1) or 1200 mg/d (Group 2). Treatment randomized to 7- days of Rifaximin 1600 mg/d (Group 1) or 1200 mg/d (Group 2). Objective measurements: Objective measurements: – GBT 1 month after treatment – Compliance – Side effects Scarpellini E, et al. Aliment Pharm Ther. 2007;25:

6 Results Drop outs: 1 patient in group 1 Drop outs: 1 patient in group 1 GBT normalization GBT normalization – Group 1 > Group 2 (80% vs. 58%; p Group 2 (80% vs. 58%; p < 0.05 ITT model) and (82% vs. 61%; p<0.05 PP). Compliance: NS difference Compliance: NS difference Side effect profile: NS difference. Side effect profile: NS difference. Scarpellini E, et al. Aliment Pharm Ther. 2007;25:

7 Conclusions This study demonstrates that Rifaximin 1600 mg/d had significantly higher efficacy for treatment of SIBO than 1200mg/d. This study demonstrates that Rifaximin 1600 mg/d had significantly higher efficacy for treatment of SIBO than 1200mg/d. Compliance rates and side effects with Rifaximin 1600 mg/d compared favorably with 1200 mg/d. Compliance rates and side effects with Rifaximin 1600 mg/d compared favorably with 1200 mg/d. Scarpellini E, et al. Aliment Pharm Ther. 2007;25:

8 Reviewer Comments This is a simple dose ranging trial to evaluate efficacy, compliance and safety of Rifaximin at 1600 mg/d vs mg/day. This is a simple dose ranging trial to evaluate efficacy, compliance and safety of Rifaximin at 1600 mg/d vs mg/day. It is likely that future studies examining treatment of IBS patients with SIBO will be conducted using this higher dose of Rifaximin that appears to be safe and more effective. It is likely that future studies examining treatment of IBS patients with SIBO will be conducted using this higher dose of Rifaximin that appears to be safe and more effective. Scarpellini E, et al. Aliment Pharm Ther. 2007;25: