Non-absorbed Antibiotics for IBS

Abstract

A recent manuscript [1] described two multi-center, prospective, double blind trials of the non-absorbed antibiotic rifaximin for nonconstipated irritable bowel syndrome (IBS). This effort adds to the body of literature from other, smaller studies that have demonstrated clinical efficacy for IBS with rifaximin. Non-absorbed antibiotics have been endorsed by the American College of Gastroenterology IBS Task Force as potentially useful therapy for IBS [2]. Interest in this approach stems from the increasing recognition of enteric bacterial imbalances in some patients with IBS compared to non-IBS controls [3][4]. An early study of antibiotics for IBS involved 87 patients with IBS randomized to rifaximin 400 mg three times daily for 10 days or placebo. During the initial 2 weeks of therapy and the subsequent 10 weeks of follow-up, rifaximin resulted in statistically significantly greater improvement in IBS symptoms than placebo [5]. The report by Pimentel et al. represents a significant advance in our knowledge and understanding of the effects of rifaximin for IBS.Clinical trials evaluating therapies for IBS are difficult to conduct and the results must be interpreted carefully. While IBS is a common condition, it is also a very subjective one, with no identified or reliable biomarkers. Thus, the diagnosis of IBS is made after careful exclusion of other pathophysiological disturbances that could result in the hallmark symptoms of abdominal pain accompanying altered bowel habits and application of symptom-based criteria such as the Rome diagnostic criteria for IBS [6][7][8]. Therein lays one of the difficulties in IBS research. The Rome criteria continue to evolve based on updated and accumulated research surrounding the pathophysiology and diagnostic approaches to IBS. The difficulty in adhering to a single diagnostic criterion, over time, among studies of IBS therapies limits the conclusions that can be drawn from the results of these studies when considered in the larger context of the IBS therapeutic milieu. Because IBS is a subjective condition, the severity from patient to patient is widely variable. Establishing reliable and reproducible barometers for determining severity of IBS symptoms and their impact are sorely needed as inclusion of patients with differing degrees of severity could affect the results of clinical trials of therapeutic agents and lead to the promotion of misleading conclusions that may not translate to clinical practice. Severity of patients in clinical trials is also paramount to consider when transferring the therapeutic approaches from trials into routine clinical practice. Additionally, the clinical endpoints of IBS therapeutic trials can be a difficult maze to negotiate. Some trials have evaluated the effects of therapy on individual IBS symptoms while others use a composite IBS score or global response as their measure of efficacy. Still others use physiologic, rather than clinical, endpoints. Over the last decade, the Food and Drug Administration has favored a global IBS endpoint fo...