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Volume 5, Supplement 1, 2005

Volume 5, Supplement 1, 2005

Table of Contents

Role of Antibiotics in Hepatic Encephalopathy: Current Status and Future Directions Introduction
This article explores the rationale for use of antibiotics in the treatment of hepatic encephalopathy, discusses the role of antibiotics relative to other therapeutic approaches, and considers the reasons that limit the use of the antibiotics most commonly prescribed for the management of hepatic encephalopathy in the United States. Although the scientific rationale for the use of antibiotics in hepatic encephalopathy is well founded, the clinical evidence for their benefits is rather limited. There is no doubt that many antibiotics cause a decrease in intraluminal production of ammonia. However, the commonly prescribed antibiotics are also associated with a variety of adverse effects. None of the antibiotics typically used for hepatic encephalopathy is adequately tolerated in the target patient population. The clinical evidence to date does not support the first-line use of currently available antibiotics in the treatment of hepatic encephalopathy. To improve upon current antibiotic offerings for hepatic encephalopathy, an antibiotic should provide broad-spectrum coverage against both aerobic and anaerobic bacteria, effectively control neuropsychiatric signs and symptoms, and be extremely well tolerated in the target population. An antibiotic fulfilling these criteria would constitute an advance in therapy for hepatic encephalopathy. [Rev Gastroenterol Disord. 2005;5(suppl 1):S3-S9]
Role of Antibiotics in the Management of Hepatic Encephalopathy
This article explores the rationale for use of antibiotics in the treatment of hepatic encephalopathy, discusses the role of antibiotics relative to other therapeutic approaches, and considers the reasons that limit the use of the antibiotics most commonly prescribed for the management of hepatic encephalopathy in the United States. Although the scientific rationale for the use of antibiotics in hepatic encephalopathy is well founded, the clinical evidence for their benefits is rather limited. There is no doubt that many antibiotics cause a decrease in intraluminal production of ammonia. However, the commonly prescribed antibiotics are also associated with a variety of adverse effects. None of the antibiotics typically used for hepatic encephalopathy is adequately tolerated in the target patient population. The clinical evidence to date does not support the first-line use of currently available antibiotics in the treatment of hepatic encephalopathy. To improve upon current antibiotic offerings for hepatic encephalopathy, an antibiotic should provide broad-spectrum coverage against both aerobic and anaerobic bacteria, effectively control neuropsychiatric signs and symptoms, and be extremely well tolerated in the target population. An antibiotic fulfilling these criteria would constitute an advance in therapy for hepatic encephalopathy. [Rev Gastroenterol Disord. 2005;5(suppl 1):S3-S9]
Rifaximin, a Nonabsorbed Oral Antibiotic, in the Treatment of Hepatic Encephalopathy: Antimicrobial Activity, Efficacy, and Safety
The nonabsorbed ( 0.4%) oral antibiotic rifaximin, which has been available for enteric bacterial conditions for more than a decade in several countries outside the United States, was recently introduced in the United States for the treatment of travelers’ diarrhea, and is being evaluated in clinical trials for possible introduction for hepatic encephalopathy and other conditions involving enteric bacteria. This article discusses the antimicrobial activity, efficacy, and safety of rifaximin in hepatic encephalopathy. Rifaximin is a nonsystemic antibiotic with antibacterial activity against enteric pathogens for gastrointestinal infections. In 15 studies, several of which were adequately powered to assess efficacy, rifaximin was at least as effective as lactulose/ lactitol (the current mainstay of pharmacologic treatment for hepatic encephalopathy) and neomycin and paromomycin (the antibiotics most commonly prescribed for hepatic encephalopathy) in improving neurologic signs and symptoms and reducing blood ammonia levels. The results of studies employing small samples are similar to those of the larger studies. Finally, rifaximin has a good tolerability profile in patients with hepatic encephalopathy, and thus appears to constitute a promising new option for this disorder. The current database on rifaximin would be strengthened by results of placebo-controlled studies to quantify more precisely the benefits of therapy. [Rev Gastroenterol Disord. 2005;5(suppl 1):S10-S18]