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Volume 5, Supplement 3, 2005

Volume 5, Supplement 3, 2005

Table of Contents

Bacterial Concepts in Irritable Bowel Syndrome Paradigm Shifts in GI Disease Management
An overlap of symptoms in irritable bowel syndrome (IBS) exists across subtype groups. Symptoms include intestinal gas, diarrhea, dyspepsia, bloating, abdominal pain, and constipation. The unifying symptom may be excessive intestinal gas as a by-product of intestinal microbial fermentation. Abnormal fermentation of food takes place when gut microbes expand proximally into the small intestine instead of being confined predominantly to the colon. Such proximal expansion of indigenous gut microbes or small intestinal bacterial overgrowth (SIBO) may lead to activation of host mucosal immunity and an increase in intestinal permeability to result in flu-like extra-intestinal symptoms that accompany the classic IBS symptoms of altered bowels. The presence of methane on lactulose breath testing is associated with constipation-predominant IBS. Antibiotic therapy may be appropriate to treat underlying SIBO in IBS patients. Seventy-five percent improvement of IBS symptoms was reported in a double-blind, placebo-controlled study once antibiotics succeeded in treating bacterial overgrowth. Once a good clinical response and normalization of the lactulose breath test are achieved, a prokinetic agent may be used to stimulate phase III of interdigestive motility to delay relapse of bacterial overgrowth. [Rev Gastroenterol Disord. 2005;5(suppl 3):S3-S9]
Role of Antibiotics in the Management of Inflammatory Bowel Disease: A Review Paradigm Shifts in GI Disease Management
The current model of pathogenesis for inflammatory bowel disease (IBD) is a dysregulated immune system that is triggered by an environmental factor in a genetically susceptible individual. Although much about this model remains unproven, it is believed that bacteria are often the environmental factor driving the inflammatory response. This is supported by indirect evidence that antibiotics are of benefit in the treatment of Crohn’s disease (CD) and pouchitis, and observations that enteric infections may result in activation of ulcerative colitis disease activity. In CD, limited studies have demonstrated that metronidazole, ciprofloxacin, and rifaximin improve clinical disease activity, and this is more pronounced in the treatment of colonic disease and for perianal fistulas (with metronidazole and ciprofloxacin). In addition, limited evidence supports the use of metronidazole in the prevention of recurrence after resection in CD. Antibiotics have not shown substantial benefit in the treatment of ulcerative colitis, but a variety of antimicrobial agents have a definite role in the treatment of acute and recurrent or chronic pouchitis. The absence of specifically identified organisms that are primarily responsible for the observed clinical picture remains the challenge to confirming the relationship between bacteria and IBD. A proposal for future therapies is provided that might include a combination therapy aimed at both a reduction in pathogenetic bacteria and immune modulation to achieve the most durable remission of disease. [Rev Gastroenterol Disord. 2005;5(suppl 3):S10-S15]
New Issues in Infectious Diarrhea Paradigm Shifts in GI Disease Management
Infectious diarrhea remains a leading cause of both mortality and morbidity worldwide. Novel organisms recently have been described as causes of previously undiagnosed diarrhea. In addition, changes in epidemiologic trends of known pathogens, such as Clostridium difficile, are occurring, including multiple outbreaks of a newly recognized epidemic strain associated with increased severity of cases and poor response to current antibiotics. Given rising resistance rates, new antimicrobial agents are being studied. Rifaximin is a nonabsorbable, gut-selective antibiotic recently approved by the US Food and Drug Administration for the treatment of travelers’ diarrhea caused by noninvasive Escherichia coli. This novel antibiotic has also shown promise in the prevention of travelers’ diarrhea, as well as a host of other gastrointestinal disorders. Development of a vaccine against diarrheagenic organisms is of high global importance but has been a challenge, owing to the multiple causative serotypes of E. coli and other organisms. [Rev Gastroenterol Disord. 2005;5(suppl 3):S16-S25]
Antibiotics in the Management of Hepatic Encephalopathy: An Evidence-Based Review Paradigm Shifts in GI Disease Management
Hepatic encephalopathy (HE) is an increasingly prevalent and debilitating condition that occurs in functional hepatic insufficiency. It is marked by fluctuating neuropsychiatric and cognitive impairment, which can be severe and life threatening. Hepatic encephalopathy is a diagnosis of exclusion; thus, it is challenging to diagnose definitively and to investigate in clinical trials. High response rates in the placebo arms of well-conducted studies demonstrate that the most effective treatment for HE is the correction of known precipitating triggers. However, pharmacological therapies may also be helpful. Although the precise pathogenesis remains unknown, bacterially derived neurotoxins from enteric flora likely play an important role. Based on this hypothesis and on accumulating clinical experience documented in randomized trials, oral antibiotics have emerged as an important treatment adjunct. This article addresses the qualities of an ideal antibiotic and reviews the literature on 4 antibiotics used to treat HE: neomycin, metronidazole, vancomycin, and rifaximin, with the most promising of these drugs appearing to be rifaximin. Unfortunately, most studies of the treatment of HE are difficult to interpret due to small sample sizes, methodological flaws, vulnerability to bias, and the intrinsic challenges of studying HE. Many studies have erroneously concluded that treatments are equivalent simply because no significant difference between treatment arms was detected. Consequently, the literature generally lacks definitive data from large, randomized, placebo-controlled trials. Nevertheless, the data suggest that minimally absorbed antibiotics are emerging as a safe and effective approach for the treatment of HE. [Rev Gastroenterol Disord. 2005;5(suppl 3):S26–S35]