Antibiotic exposure and the emergence of multidrug resistant bacteria in patients with liver cirrhosis: A prospective cohort study

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ID: 331997
2026
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Ranked #561 of 635 articles by views in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Abstract
BACKGROUND: Infections caused by multidrug-resistant organisms (MDROs) are a growing concern in patients with advanced chronic liver disease and acute-on-chronic liver failure, worsening clinical outcomes. Although prior antibiotic exposure is associated with resistance, prospectively defined, clinically actionable exposure thresholds in this population are lacking. We aimed to quantify cumulative-exposure thresholds for de novo MDRO acquisition and assess the prognostic impact of MDRO emergence on survival. METHODS: We prospectively enrolled 256 consecutive adults with advanced chronic liver disease at the University Hospital Frankfurt (2020-2023). Antibiotic exposure was quantified using defined daily doses (DDD) and antibiotic use density (AUD); MDRO colonisation and infection were captured by systematic microbiological surveillance. Time-to-death was analysed in a competing-risk framework with liver transplantation as competing event. RESULTS: Among 246 patients without MDRO at the first admission swab, de novo acquisition of vancomycin-resistant enterococci (VRE) or Gram-negative MDR was strongly associated with cumulative antibiotic exposure (p<0.001). The 20% probability threshold for VRE 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 at baseline, was independently associated with increased 180-day mortality (HR 2.15, 95% CI 1.27-3.64; p=0.004). CONCLUSIONS: In advanced cirrhosis, MDRO emergence is associated with cumulative antibiotic exposure beyond distinct, class-specific thresholds and carries excess mortality. These prospective findings identify cumulative antibiotic burden as a modifiable risk factor and support an exposure-aware approach to antimicrobial stewardship in this population.
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Authors Myriam W. Heilani, Toska Wiedemann, Christopher Best, Philip G Ferstl, Victoria Therese Mücke, Katharina Maria Schwarzkopf, Hans-Peter Erasmus, Kai-Henrik Peiffer, Tobias Burbach, Michael Hogardt, André Mohr, Johanna Kessel, Maria J G T Vehreschild, Stefan Zeuzem, Jonel Trebicka, Christoph Welsch, Eva Herrmann, Volkhard A. J. Kempf, Marcus Maximilian Mücke
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Journal Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Year 2026
DOI
10.1093/cid/ciag610
URL
https://doi.org/10.1093/cid/ciag610
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