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<p>Antibiotic therapy is essential for sepsis management, but the optimal empirical strategy remains uncertain. This study evaluated the effects of first-line antibiotic preference and initiation timing on in-hospital mortality among intensive care units (ICU) patients with sepsis. Using the MIMIC-IV database, we emulated a sequential target trial comparing patients who received antibiotics within 48&#xa0;h of sepsis diagnosis versus delayed initiation. Randomization was approximated through a clone–censor–weight process to address confounding by indication. The primary outcome was in-hospital mortality. Weighted Cox regression estimated hazard ratios (HRs), and sensitivity analyses tested robustness. Among 3,669 eligible patients, 3,568 (97%) received antibiotics within 48&#xa0;h. After weighting, covariate balance was achieved. Beta-lactam use was associated with lower in-hospital mortality (HR 0.88, 95% CI 0.78–0.95), with consistent reductions at 7, 14, and 60 days. Timing within the 48-hour window did not modify outcomes for either beta-lactams or glycopeptides. Empirical beta-lactam therapy was linked to improved survival among ICU sepsis patients, whereas timing of initiation showed no significant impact. These findings support prioritizing beta-lactam–based regimens as first-line empirical coverage in early sepsis management.</p>

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Association of antibiotic type and timing with sepsis mortality using target trial emulation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月25日

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  • Jiayang Li,
  • Mingyi Zhao,
  • Qingnan He

摘要

Antibiotic therapy is essential for sepsis management, but the optimal empirical strategy remains uncertain. This study evaluated the effects of first-line antibiotic preference and initiation timing on in-hospital mortality among intensive care units (ICU) patients with sepsis. Using the MIMIC-IV database, we emulated a sequential target trial comparing patients who received antibiotics within 48 h of sepsis diagnosis versus delayed initiation. Randomization was approximated through a clone–censor–weight process to address confounding by indication. The primary outcome was in-hospital mortality. Weighted Cox regression estimated hazard ratios (HRs), and sensitivity analyses tested robustness. Among 3,669 eligible patients, 3,568 (97%) received antibiotics within 48 h. After weighting, covariate balance was achieved. Beta-lactam use was associated with lower in-hospital mortality (HR 0.88, 95% CI 0.78–0.95), with consistent reductions at 7, 14, and 60 days. Timing within the 48-hour window did not modify outcomes for either beta-lactams or glycopeptides. Empirical beta-lactam therapy was linked to improved survival among ICU sepsis patients, whereas timing of initiation showed no significant impact. These findings support prioritizing beta-lactam–based regimens as first-line empirical coverage in early sepsis management.