Rifaximin discontinuation during broad-spectrum antibiotic treatment in critically ill patients with hepatic encephalopathy

Hepatic encephalopathy (HE) is one of the main complications of cirrhosis, characterized by a wide spectrum of neuropsychiatric alterations that lead to an increase in mortality, morbidity and recurrent hospitalizations. Due to the central role in HE pathogenesis of ammonia and other neurotoxins primarily produced by the gut microbiota, the main therapeutic approaches for the treatment of HE are based on the modulation of the gut microbiota. Rifaximin is a non-absorbable broad-spectrum antibiotic, that is effective against ammonia-producing gram-positive, gram-negative, and anaerobic species, approved for the treatment of HE in secondary prophylaxis. The chronic administration of rifaximin in this setting is associated with a lower risk of HE recurrence and mortality, while the role of rifaximin for the treatment of an overt-HE episode in inpatients is still unclear. Limited data exist about the coadministration of rifaximin and broad-spectrum antibiotics commonly used to treat concomitant infections, as patients receiving or recently treated with antibiotics were frequently excluded from clinical trials. In this editorial we comment on the article by Ward <i>et al</i> published in the recent issue of the <i>World Journal of Hepatology</i>. It is a single center, retrospective, quasi-experimental, pharmacist-driven protocol, with the aim to evaluate the feasibility and safety of rifaximin discontinuation in critically ill patients with HE and chronic liver disease receiving broad-spectrum antibiotic therapies in intensive care units. The study revealed no differences between the protocol and control group in terms of primary outcome (days alive and free of delirium and coma to day 14) and secondary outcomes which include: Intensive care mortality, intensive care length of stay, intravenous vasopressor requirement changes and adverse effects rate. Therefore, rifaximin discontinuation during broad-spectrum antibiotic therapy does not appear to negatively impact the clinical status of critically ill liver patients, with a similar safety profile and significant cost savings, as compared to the coadministration of rifaximin and broad-spectrum antibiotics. In agreement with Ward <i>et al</i>, a recently published double-blind, randomized controlled trial provided additional evidence to support the feasibility of withholding rifaximin during broad-spectrum antibiotic therapy in critically ill cirrhotic patients. However, given the limitations of these studies, further multicentric and prospective clinical trials, enrolling a larger sample of non-critically ill patients, are needed to better establish the role of rifaximin in this setting.