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 pre-admission rifaximin use.Methods: From the global CLEARED consortium, we focused on cirrhosis inpatients with infections on/during admission.Clinical/demographic/medications especially rifaximin details were recorded.The primary outcome was DRO development.Multivariable regression for DRO development including clinical, medications, and country income were 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),AKI/HRS (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<0.0001) without difference in rifaximin use (1.4 vs.1.7%,p=0.61).On adjusted analysis, MELD-Na (1.03,95% CI:1.02-1.04,p<0.001)increased, whereas male sex (0.73,95%CI:0.58-0.92,p=0.008)and HBV (0.65,95%CI:0.45-0.92,p=0.020)decreased DRO.Rifaximin was not associated with DROs overall (OR:1.07,95%CI:0.80-1.43,p=0.65) or within income strata (High:1.07,95%CI:0.59-1.92,p=0.82,Upper-middle:1.18,95%CI:0.74-1.85,p=0.49,low/lowmiddle:1.04,95%CI:0.60-1.81,p=0.90)despite sensitivity analyses.Conclusion: In this large global cohort of hospitalized patients with cirrhosis and infections, 12% developed infections involving DROs.30% had pre-admission rifaximin use which was not linked with daptomycin use, or with with DRO development on adjusted analysis overall or across country income groups.