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Introduction <p>The survival benefit of early antibiotic administration in septic shock is well established. In contrast, for sepsis without shock, the current Surviving Sepsis Campaign (SSC) guidelines recommend initiating antibiotics according to the likelihood of infection. Given the persistent challenges in accurately diagnosing sepsis, there is a need to identify patient characteristics to guide antimicrobial timing in this population.</p> Methods <p>In this cohort study, we included adult intensive care unit (ICU) patients meeting Third International Consensus Definitions for Sepsis (Sepsis-3) criteria without shock, identified from 24&#xa0;hours before to 48&#xa0;hours after ICU admission, who received antibiotics within 0–12&#xa0;hours after sepsis diagnosis. The primary exposure was shorter time-to-antibiotics (≤&#xa0;3&#xa0;hours), and the primary outcome was 28-day mortality. Heterogeneity of treatment effect (HTE) was evaluated with conventional subgroup, risk-based, and effect-based analyses.</p> Results <p>A total of 8400 patients were included, of whom 2891 (34.4%) received antibiotics within 3&#xa0;hours and emergency admission was the most common admission type (64.2%). Baseline characteristics were well balanced after overlap weighting. Shorter time-to-antibiotics was not associated with 28-day mortality in the overall population (median value for the posterior distribution of the odds ratio (OR) 0.92; 95% credible interval (CrI) 0.79–1.06). In conventional subgroups, the impact of shorter time-to-antibiotics on 28-day mortality varied substantially between patients aged ≥&#xa0;78&#xa0;years and other age subgroups (median value for the posterior distribution of the OR 0.73; 95% CrI 0.55–0.94). In risk-based analysis, patients in the third quartile of baseline mortality risk exhibited the most favorable estimated association with shorter time-to-antibiotics (median value for the posterior distribution of the OR 0.65; 95% CrI 0.46–0.87). In effect-based analysis, patients with advanced age, higher Charlson Comorbidity Index (CCI), higher Acute Physiology Score&#xa0;III (APS&#xa0;III), or acute liver dysfunction were identified as having greater benefit from shorter time-to-antibiotics.</p> Conclusion <p>Among ICU patients with sepsis without shock, those who are older, have higher CCI or APS&#xa0;III, or acute liver dysfunction are more likely to benefit from shorter time-to-antibiotics.</p>

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Early Antibiotic Therapy in Sepsis Without Shock: A Multimethod Study of Heterogeneous Treatment Effects in ICU Patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月19日

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  • Peng Zhang,
  • Tongkun Zuo,
  • Xingxing Zhu,
  • Jilou Wei,
  • Min Wang,
  • Xiangcheng Zhang,
  • Ying Huang

摘要

Introduction

The survival benefit of early antibiotic administration in septic shock is well established. In contrast, for sepsis without shock, the current Surviving Sepsis Campaign (SSC) guidelines recommend initiating antibiotics according to the likelihood of infection. Given the persistent challenges in accurately diagnosing sepsis, there is a need to identify patient characteristics to guide antimicrobial timing in this population.

Methods

In this cohort study, we included adult intensive care unit (ICU) patients meeting Third International Consensus Definitions for Sepsis (Sepsis-3) criteria without shock, identified from 24 hours before to 48 hours after ICU admission, who received antibiotics within 0–12 hours after sepsis diagnosis. The primary exposure was shorter time-to-antibiotics (≤ 3 hours), and the primary outcome was 28-day mortality. Heterogeneity of treatment effect (HTE) was evaluated with conventional subgroup, risk-based, and effect-based analyses.

Results

A total of 8400 patients were included, of whom 2891 (34.4%) received antibiotics within 3 hours and emergency admission was the most common admission type (64.2%). Baseline characteristics were well balanced after overlap weighting. Shorter time-to-antibiotics was not associated with 28-day mortality in the overall population (median value for the posterior distribution of the odds ratio (OR) 0.92; 95% credible interval (CrI) 0.79–1.06). In conventional subgroups, the impact of shorter time-to-antibiotics on 28-day mortality varied substantially between patients aged ≥ 78 years and other age subgroups (median value for the posterior distribution of the OR 0.73; 95% CrI 0.55–0.94). In risk-based analysis, patients in the third quartile of baseline mortality risk exhibited the most favorable estimated association with shorter time-to-antibiotics (median value for the posterior distribution of the OR 0.65; 95% CrI 0.46–0.87). In effect-based analysis, patients with advanced age, higher Charlson Comorbidity Index (CCI), higher Acute Physiology Score III (APS III), or acute liver dysfunction were identified as having greater benefit from shorter time-to-antibiotics.

Conclusion

Among ICU patients with sepsis without shock, those who are older, have higher CCI or APS III, or acute liver dysfunction are more likely to benefit from shorter time-to-antibiotics.