Research Appraisalobservational

Clinical impact of broad- versus narrow-spectrum empiric therapy in acute cholangitis: A Japanese claims database study

PloS oneAoto, Kazuhiro, Inose, Ryo, Muraki, YuichiDOI

Clinical Snapshot

80CEBM
Evidence: Moderateobservational

PICO Framework

P — PopulationAdult patients (18-99 years) diagnosed with acute cholangitis who received antibiotics, had blood cultures collected, and underwent biliary drainage in Japan (2014-2022)
I — InterventionBroad-spectrum empiric antibiotic therapy (carbapenems, piperacillin/tazobactam, or fourth-generation cephalosporins)
C — ComparatorNarrow-spectrum empiric antibiotic therapy (other antibiotics not classified as broad-spectrum)
O — OutcomesPrimary: 30-day in-hospital mortality; Secondary: duration of intravenous antibiotic therapy and length of hospital stay

Bottom Line

This large Japanese claims database study of 4,755 patients with acute cholangitis found no mortality benefit from broad-spectrum empiric antibiotic therapy compared to narrow-spectrum alternatives. Patients receiving broad-spectrum therapy (carbapenems, piperacillin/tazobactam, fourth-generation cephalosporins) had similar 30-day mortality rates but longer antibiotic courses and hospital stays. The findings support antimicrobial stewardship principles favouring narrow-spectrum empiric therapy in acute cholangitis, though clinicians should consider local resistance patterns and individual patient factors. The study's retrospective design and Japanese setting limit direct applicability to Australian practice, but the results align with global efforts to reduce unnecessary broad-spectrum antibiotic use while maintaining clinical effectiveness.

Evidence: Moderate

Key Findings

  • P Value: Not significant (confidence intervals cross 1.0)

  • Effect Size: Adjusted OR 1.37 (multivariate); OR 1.43 (propensity score matched)

  • Primary Outcome: 30-day in-hospital mortality

  • Nnt Or Sensitivity: No significant mortality benefit; broad-spectrum group had 1 day longer IV antibiotic duration and 3 days longer hospital stay

  • Confidence Interval: 95% CI 0.84-2.23 (multivariate); 95% CI 0.82-2.50 (PSM)

Clinical Application

Highly feasible - supports current antimicrobial stewardship principles favouring narrow-spectrum therapy when appropriate Relevant to Australian practice but requires consideration of local resistance patterns. Supports TGA antimicrobial stewardship guidelines and may inform PBS antibiotic prescribing decisions Adult patients with acute cholangitis requiring empiric antibiotic therapy and biliary drainage

Abstract

The clinical benefit of broad-spectrum empiric therapy in patients with acute cholangitis is unclear. We aimed to evaluate the impact of broad-spectrum and narrow-spectrum empiric therapies on patient outcomes using a Japanese claims database. The study included patients who were diagnosed with acute cholangitis between April 2014 and August 2022, aged 18-99 years, received antibiotics, had blood cultures collected, and underwent biliary drainage. Patients who received empiric therapy with carbapenems, piperacillin/tazobactam, or fourth-generation cephalosporins were included in the broad-spectrum group, whereas others were included in the narrow-spectrum group. Of the 4,755 eligible patients, 3,377 were categorized into the narrow-spectrum group and 1,378 into the broad-spectrum group. In the multivariate logistic regression analysis, older age, higher Charlson Comorbidity Index, the presence of sepsis, and intensive care unit admission were associated with increased 30-day in-hospital mortality, whereas the receipt of broad-spectrum empiric therapy was not (adjusted odds ratio, 1.37 [95% confidence interval {CI}, 0.84-2.23]). In the propensity score matching analysis, there was also no association between the receipt of broad-spectrum empiric therapy and 30-day in-hospital mortality (odds ratio, 1.43 [95% CI, 0.82-2.50]). Furthermore, in the propensity score-matched cohort, the broad-spectrum group had longer duration of intravenous antibiotic therapy (median interquartile range [IQR]: 8 [6 -11] day vs. 9 [7 -13] day; difference 1 day [95% CI, 0.31-1.69 day]) and length of hospital stay (median [IQR]: 13 [9 -20] day vs. 16 [11 -25] day; difference 3 day [95% CI, 1.87-4.13 day]), compared with the narrow-spectrum group. In this large-scale study using a Japanese claims database, broad-spectrum empiric therapy was not associated with improved clinical outcomes, compared with narrow-spectrum empiric therapy. Therefore, the necessity of broad-spectrum empiric therapy may be limited in clinical practice, and narrow-spectrum empiric therapy may represent an effective treatment strategy for acute cholangitis.

References

  1. 1.Aoto, K., Inose, R., & Muraki, Y. (2026). Clinical impact of broad- versus narrow-spectrum empiric therapy in acute cholangitis: A Japanese claims database study. PLoS One. https://doi.org/10.1093/ofid/ofaf298
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