Letter to the Editor
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 27, 2024; 16(11): 1356-1360
Published online Nov 27, 2024. doi: 10.4254/wjh.v16.i11.1356
Rifaximin discontinuation during broad-spectrum antibiotic treatment in critically ill patients with hepatic encephalopathy
Lorenzo Ridola, Alessandro Mari
Lorenzo Ridola, Alessandro Mari, Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Rome 00185, Italy
Author contributions: Mari A was responsible for conceptualization and manuscript writing; Ridola L was responsible for conceptualization, manuscript writing, key revisions of important knowledge content, and final approval.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Lorenzo Ridola, PhD, Associate Professor, Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Viale dell'Università 37, Rome 00185, Italy. lorenzo.ridola@uniroma1.it
Received: May 27, 2024
Revised: October 1, 2024
Accepted: October 23, 2024
Published online: November 27, 2024
Processing time: 162 Days and 18.1 Hours
Abstract

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 et al published in the recent issue of the World Journal of Hepatology. 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 et al, 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.

Keywords: Hepatic encephalopathy; Rifaximin discontinuation; Broad-spectrum antibiotics; Critically ill patients; Intensive care unit

Core Tip: According to the current international guidelines, rifaximin administration is recommended only for the secondary prophylaxis of recurrent hepatic encephalopathy (HE). The rifaximin role for the treatment of an overt HE episode in inpatients is still unclear. However, in clinical practice, it is common to keep on rifaximin therapy that patients were already on prior to hospitalization during an overt HE episode. The Ward et al study demonstrated for the first time the feasibility and safety of rifaximin discontinuation during broad-spectrum antibiotic therapy, with significant cost saving during hospitalization.