TOPLINE

In patients with advanced chronic liver disease, cumulative antibiotic exposure was associated with new acquisition of multidrug-resistant organisms, particularly vancomycin-resistant enterococci. Newly detected multidrug-resistant organisms during follow-up, but not at baseline, were independently associated with a higher risk for 180-day mortality.

METHODOLOGY

• Researchers conducted a prospective cohort study to quantify the cumulative antibiotic exposure associated with new acquisition of multidrug-resistant bacteria and to assess whether newly detected resistant bacteria were linked to 180-day mortality in patients with advanced chronic liver disease.
• The analysis included 256 patients treated at a German center from 2020 to 2023 (median age, 59 years; 68.8% men), and antibiotic exposure was analyzed among the 246 patients who had no multidrug-resistant bacteria on their first admission swab.
• Cumulative antibiotic exposure was the total in-hospital dose per patient, counted up to the first detection of multidrug-resistant bacteria or across the full follow-up if no multidrug-resistant bacteria were found, and measured in defined daily doses and as antibiotic use per 100 patient-days.
• Resistant bacteria were detected using oral and rectal screening swabs taken at admission, at every readmission, and when clinically indicated.
• The researchers also estimated the cumulative antibiotic dose (overall and by drug class) at which the probability of acquisition reached 20% and 40%.

TAKEAWAY

• During follow-up, 49 of 246 patients (19.9%) acquired vancomycin-resistant enterococci and 28 (11.4%) acquired resistant Gram-negative bacteria.
• The estimated risk for vancomycin-resistant enterococci acquisition reached 20% at 9.6 cumulative defined daily doses of any antibiotic and at lower doses for individual classes — 3.3 for carbapenems, 3.0 for cephalosporins, 1.5 for glycopeptides, and 3.6 for piperacillin-tazobactam. For Gram-negative multidrug-resistant bacteria, the 20% thresholds were 19.2 for any antibiotic, 8.9 for beta-lactam/beta-lactamase inhibitor combinations, 9.9 for piperacillin-tazobactam, and 7.0 for carbapenems.
• After adjustment, newly detected resistant bacteria during follow-up were associated with a higher risk for 180-day mortality (hazard ratio, 2.15; P =.004), whereas resistant bacteria detected on the first admission swab were not.
• Patients who acquired vancomycin-resistant enterococci had higher overall antibiotic exposure than those who did not, based on both defined daily doses and antibiotic use density (P < .001). Among patients who acquired Gram-negative multidrug-resistant bacteria, only imipenem exposure was significantly higher (P < .05).

IN PRACTICE

″[O]ur results support an exposure-aware approach in decompensated cirrhosis: cumulative exposure — not only fixed duration — should inform daily decisions, with class-specific guidance prompting timely reassessment, narrowing, or de-escalation,″ the authors wrote.

SOURCE

The study was led by Myriam W. Heilani, Goethe University Frankfurt, Frankfurt am Main, Germany. It was published online on October 9, 2026, in Clinical Infectious Diseases.

LIMITATIONS

Residual confounding from disease severity was possible as patients with more severe illness received more antibiotics and were tested more often. Antibiotics given outside the study hospital were not recorded, which may have led to underestimation of exposure. The dose thresholds came from one center and needed validation in other settings.

DISCLOSURES

The study was supported by the German Research Foundation, the German Federal Ministry of Education and Research, and the Hessian Ministry of Higher Education, Research and the Arts. Several authors reported receiving speaker, consulting, or advisory fees, travel support, or research grants from various companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.