Rifaximin in cirrhosis: when therapeutic drift meets antimicrobial stewardship

This Viewpoint examines the evolving role of rifaximin in cirrhosis, arguing that therapeutic drift has outpaced evidence and antimicrobial stewardship. While rifaximin is effective for secondary prevention of recurrent overt hepatic encephalopathy, randomised trials have failed to demonstrate benefit for primary prevention of hepatic encephalopathy, prevention of acute-on-chronic liver failure, or broader disease modification. Concurrently, emerging microbiological and epidemiological data challenge the perception of rifaximin as a benign gut modulator. Prolonged exposure is associated with selection of antimicrobial resistance genes, rifaximin-resistant Enterobacter spp, and cross-resistance in Enterococcus faecium to last-line agents such as daptomycin. In a population already highly susceptible to multidrug-resistant infections and adverse transplant outcomes, this association with antimicrobial resistance raises important public health concerns. We argue for a recalibration of rifaximin use to evidence-based indications and for embedding antimicrobial stewardship principles within hepatology guidelines and policy.