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Lack of association between rifaximin and drug-resistant infections: a global multicenter inpatient cirrhosis cohort
Jasmohan S Bajaj1, Patrick S Kamath2, Florence Wong3
1Department of Medicine, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, USA. jasmohan.bajaj@vcuhealth.org.
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.
Insights
Drug-resistant organism infections are common in cirrhosis patients. Pre-admission rifaximin use did not increase the risk of drug-resistant organism infections in a global study of hospitalized cirrhosis patients.
Area of Science:
- Hepatology
- Infectious Diseases
- Pharmacology
Background:
- Drug-resistant organisms (DROs) pose a significant threat to patients with cirrhosis, leading to adverse outcomes.
- Rifaximin, a common treatment for hepatic encephalopathy (HE), raises concerns about potential cross-resistance, but clinical evidence remains inconclusive.
Purpose of the Study:
- To identify predictors of DRO development in a diverse global cohort of hospitalized cirrhosis patients.
- To specifically investigate the association between pre-admission rifaximin use and the incidence of DROs.
Main Methods:
- Analysis of data from the global CLEARED consortium, focusing on cirrhosis inpatients with infections.
- Collection of detailed clinical, demographic, and medication data, with a focus on rifaximin use.
- Multivariable regression analysis to determine factors associated with DRO development, including country income levels.
Main Results:
- 12.2% of all infections and 24.4% of culture-positive infections in the cohort involved DROs.
- Pre-admission rifaximin use was reported in 29.7% of patients, predominantly for HE management, and was associated with more advanced cirrhosis.
- Adjusted analysis revealed no significant association between rifaximin use and DRO development overall (OR: 1.07) or across different country income strata.
Conclusions:
- Infections with drug-resistant organisms are prevalent in hospitalized cirrhosis patients.
- Pre-admission rifaximin use was not found to be an independent predictor of DRO development in this global cohort.
- Findings suggest that rifaximin use, even prior to hospitalization, does not significantly increase the risk of DRO infections in cirrhosis patients.
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