Jasmohan S Bajaj, Patrick S Kamath, Florence Wong, Qing Xie, Ramazan Idılman, Mark Topazian, Wai-Kay Seto, Aldo Torre, PC Hayes, Jacob George, Mario Silva, Brian J. Bush, Scott Silvey, Ashok Choudhury, On behalf of the EXPLANTORREDO-TAVR Registry Investigators
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.