Lack of association between rifaximin and drug-resistant infections: a global multicenter inpatient cirrhosis cohort
Year: 2026
Type: article
Study design: Observational Study
Abstract: 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<0.0001) without a 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 hepatitis-B (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/low-middle: 1.04, 95% CI 0.60-1.81, P=0.90) despite sensitivity analyses. CONCLUSIONS: 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 DRO development on adjusted analysis overall or across country income groups.
Authors: Jasmohan S. Bajaj, Patrick S. Kamath, Florence Wong, Qing Xie, Ramazan Idilman, Mark Topazian, Wai-Kay Seto, Aldo Torre, Peter Hayes, Peter George, Mario Alvares-da-Silva, Brian J. Bush, Scott Silvey, Ashok Choudhury, on behalf of CLEARED Investigators
Institutions: Virginia Commonwealth University, Hunter Holmes McGuire VA Medical Center, Virginia Commonwealth University Medical Center, Mayo Clinic, University of Toronto, Shanghai Jiao Tong University, Ruijin Hospital, Ankara University, St. Paul's Hospital Millennium Medical College, University of Hong Kong, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, University of Edinburgh, The University of Sydney, Westmead Hospital, Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre, Institute of Liver and Biliary Sciences
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $32
Funder: National Institutes of Health
OpenAlex ID: W7154446284