Patients enrolled did not have any current evidence of HE at inclusion. The main study outcomes Lumacaftor were the occurrence of clear episodes of HE: a more objective endpoint than the amelioration of HE symptoms in patients already affected by HE at inclusion. Rifaximin is a semisynthetic, gut-selective antibiotic whose mechanism of antimicrobial action depends on inhibition of RNA synthesis.8, 9 There are several lines of evidence that rifaximin has poor solubility and is poorly absorbed, which results in a gut-specific action. In healthy individuals, as much as 97% of radiolabeled rifaximin is recovered; 96% in the stool and

only 0.32% in the urine.10 The systemic exposure to rifaximin in patients with Child A, B, and C cirrhosis compared to rifampin and neomycin is shown in Fig. 1.10 Dosing of rifaximin

can be approached in two broad ways: cyclical or continuous. In Italy, cyclical dosing is preferred and several clinical trials have shown benefit with learn more rifaximin treatment 2 weeks per month.8 The alternative is daily therapy with rifaximin that is currently being used in the United States. There are possible advantages and disadvantages to each approach; cyclical therapy reduces cost and exposure to antibiotic but adherence to the schedules may be difficult in patients who already have HE. Continuous therapy is more expensive and could have the potential to increase resistance to rifaximin. The daily dose most studied, regardless of cyclical or continuous, is 1200 mg whereas the most recent trial used 1100 mg/day.6 MCE公司 In some European countries, including Italy and Spain, rifaximin is available in packages containing only 12 tablets, which is the dosage needed for just 2 days of therapy, and this also may limit the availability of the drug for long term treatment. For example, in Italy, in order

to obtain the drug by means of the public health care system, the patient should consult the prescribing practitioner every 4 days! Being a gut-selective antibiotic, the majority of the action of rifaximin is concentrated on the gut microflora. The antibacterial properties of rifaximin include bactericidal activity at rifaximin concentrations greater than or equal to the minimal inhibitory concentration (MIC); at sub-MIC concentrations, rifaximin can change functioning of epithelial cells as well as virulence of the gut bacteria.10 Several randomized, placebo-controlled trials have been performed with rifaximin, most of them in Europe.8, 10 These trials have studied short-term management of the acute episode, long-term therapy and prevention of recurrence.9 A summary of the trials with their key findings is shown in Table 1. Rifaximin has been studied in the context of intestinal pathogens and the concentration needed to inhibit 50% (MIC50) and 90% of microorganism growth (MIC90) have been established for 1607 pathogens; the highest MIC reached was 1024 μg/mL.