Lack of association between rifaximin and drug-resistant infections: a global multicenter inpatient cirrhosis cohort

BACKGROUND/AIMS: Infections with drug-resistant organisms (DROs) are associated with poor outcomes in cirrhosis. Rifaximin, widely used for hepatic encephalopathy (HE), could promote cross-resistance, but data regarding clinical impact are conflicting. Aim: Determine predictors of DROs in a global cirrhosis inpatient cohort focusing on preadmission rifaximin use. METHODS: From the global CLEARED consortium, we focused on cirrhosis inpatients with infections on/during admission. Clinical/demographic/medication, especially rifaximin details were recorded. The primary outcome was DRO development. Multivariable regression for DRO including clinical, medications, and country income was performed. RESULTS: 2,949 infected inpatients (55.3 years, 62.9% male) were included. 12.2% of all and 24.4% of culture-positive infections developed DROs; these patients had higher HE (39 vs. 31%, P=0.003), hepatorenal syndrome (25 vs. 19%, P=0.006), lactulose (55 vs. 47%, P=0.008) and rifaximin use (34 vs. 27%, P=0.006) on crude comparisons but country-income distributions were similar. 29.7% were on pre-admission rifaximin, mostly HE-related; they had more advanced cirrhosis and from low/low-middle-income countries. Daptomycin was used in 1.5%, linked with DROs (5.0 vs. 1.0%, P