Cumulative Antibiotic Exposure Tied to Multidrug-Resistant Organism Acquisition in Cirrhosis

Among patients with advanced chronic liver disease, new acquisition of multidrug-resistant organisms (MDROs) was strongly associated with cumulative antibiotic exposure, and MDRO emergence during follow-up was associated with higher 180-day mortality, according to a prospective cohort study published in Clinical Infectious Diseases.

The authors noted that although prior antibiotic exposure is associated with resistance, prospectively defined, clinically actionable thresholds for antibiotic exposure have been lacking in this population. They enrolled 256 consecutive adults with advanced chronic liver disease at University Hospital Frankfurt in Germany from 2020 to 2023. Antibiotic exposure was quantified using defined daily doses (DDDs) and antibiotic use density. MDRO colonization and infection were tracked through systematic microbiological surveillance. Mortality was analyzed in a competing-risk framework, with liver transplantation as the competing event.

Among 246 patients without an MDRO on the first admission swab, de novo acquisition of vancomycin-resistant enterococci (VRE) or multidrug-resistant Gram-negative bacteria was strongly associated with cumulative antibiotic exposure (P < .001). The 20% probability threshold for VRE acquisition was reached at 9.6 cumulative DDDs of any antibiotic, with substantially lower thresholds for β-lactam/β-lactamase inhibitor combinations, carbapenems, and glycopeptides.

De novo MDRO detection during follow-up, but not MDRO detection at baseline, was independently associated with increased 180-day mortality (hazard ratio, 2.15; 95% CI, 1.27-3.64).

The authors concluded that MDRO emergence in advanced cirrhosis is associated with cumulative antibiotic exposure above thresholds that differ by antibiotic class and is linked to excess mortality. They described cumulative antibiotic burden as a modifiable risk factor and said the results support antimicrobial stewardship that accounts for exposure in this population.

Source: Heilani MW, Wiedemann T, Best C, et al. Antibiotic exposure and the emergence of multidrug resistant bacteria in patients with liver cirrhosis: a prospective cohort study. Clin Infect Dis. Published online October 9, 2026. doi:10.1093/cid/ciag610