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.