Can rifaximin for hepatic encephalopathy be discontinued during broad-spectrum antibiotic treatment?

Abstract

Hepatic encephalopathy (HE) is a formidable complication in patients with decompensated cirrhosis, often necessitating the administration of rifaximin (RFX) for effective management. RFX, is a gut-restricted, poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE. It has shown notable reductions in infection, hospital readmission, duration of hospital stay, and mortality. However, limited data exist about the concurrent use of RFX with broad-spectrum antibiotics, because the patients are typically excluded from studies assessing RFX efficacy in HE. A pharmacist-driven quasi-experimental pilot study was done to address this gap. They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment, particularly in critically ill patients in intensive care unit (ICU). The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered. The findings also indicate that RFX discontinuation during broad-spectrum antibiotic therapy was not associated with higher rates of delirium or coma, and this result remained robust after adjustment in multivariate analysis. Furthermore, rates of other secondary clinical and safety outcomes, including ICU mortality and 48-hour changes in vasopressor requirements, were comparable. However, since the activity of RFX is mainly confined to the modulation of gut microbiota, its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable, given the overlapping antibiotic activity. Further, this suggests that the action of RFX on HE is class-specific (related to its activity on gut microbiota), rather than drug-specific. A recent double-blind randomized controlled (ARiE) trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics. Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections. Despite these compelling results, both studies have limitations. A prospective, multi-center evaluation of a larger sample, with placebo control, and comprehensive neurologic evaluation of HE is warranted. It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.

Keywords: Rifaximin discontinuation; Hepatic encephalopathy; Broad-spectrum antibiotics; Crit-ically ill; Medical intensive care unit; Pharmacist-driven protocol

Core Tip: Rifaximin (RFX) is a gut-restricted adjunct to lactulose that minimizes hepatic encephalopathy (HE) recurrence with minimal systemic absorption. Despite established benefits, limited Food and Drug Administration approval for acute HE raises concern about its use in treating acute overt HE. Recent evidence challenges the routine use of RFX with broad-spectrum antibiotics, emphasizing their class-specific effects in critically ill patients. The study sheds light on the safety of discontinuing RFX during broad-spectrum antibiotic therapy in intensive care unit patients with liver disease and HE, and also prompts reevaluation of the role of RFX amid the overlapping antibiotic activity. This evidence underscores the need for further investigations to optimize the management of both HE and systemic infections in patients with liver disease, including those who are not critically ill.