# Optimal timing of antibiotics administration for sepsis or septic shock in the emergency department

## TL;DR

Administering antibiotics within one hour of sepsis diagnosis is linked to lower in-hospital mortality, according to a large study of emergency department patients.

## Contribution

This study provides new evidence on the time-dependent relationship between antibiotic administration and mortality in sepsis patients.

## Key findings

- Patients receiving antibiotics within 1 hour had 35.9% in-hospital mortality compared to 47.4% for those treated after 1 hour.
- Adjusted analysis showed a 6.4% lower mortality risk for antibiotic administration within 1 hour.
- Mortality risk increased significantly after 3 hours, with the lowest risk observed at around 0.5 hours.

## Abstract

Early antibiotic administration is considered an important component of sepsis management, yet the optimal time-to-antibiotics (T2A) remains uncertain. This study examined the association between T2A and in-hospital mortality among patients with sepsis and septic shock and explored how this relationship varies across different time intervals.

We conducted a retrospective cohort analysis of emergency department patients with sepsis from 1998 to 2022. Patients were dichotomized into two groups (T2A ≤ 1 h vs. T2A > 1 h), and clinical characteristics and mortality outcomes were compared. Cox proportional hazards models were used to assess the association between T2A and in-hospital mortality, adjusting for illness severity and other covariates. A non-linear Cox regression model was further applied to characterize the time-dependent relationship between T2A and mortality risk.

A total of 15,317 patients were included. In-hospital mortality was 35.9% for patients receiving antibiotics within 1 h and 47.4% for those treated after 1 h (P < 0.001). After adjustment, T2A ≤ 1 h remained associated with lower mortality (adjusted HR = 0.936; 95% CI, 0.891–0.982). Non-linear modeling suggested that mortality risk was generally lower when antibiotics were administered within approximately 3 h, with the lowest estimated hazard observed at around 0.5 h; risk increased more noticeably beyond the 3-hour mark. These patterns were consistent across patients with and without septic shock.

In this large retrospective cohort, shorter time-to-antibiotics was associated with lower in-hospital mortality, with the most favorable estimates occurring within the first hour and a gradual attenuation of benefit approaching 3 h. These findings provide insight into the time-dependent relationship between antibiotic administration and outcomes in sepsis that warrants further validation before being incorporated into clinical practice recommendations.

Not applicable.

The online version contains supplementary material available at 10.1186/s12873-026-01471-5.