Increasing the door-to-antibiotic time in patients who present to the emergency department (ED) with clinical sepsis was associated with an hour-by-hour linear increase in 1-year mortality, according to a study published in CHEST.

Conflicting results from previous studies have made antibiotic timing in sepsis a controversial issue. This retrospective cohort study was designed to investigate the association between door-to-antibiotic time and long-term mortality in patients who presented to the ED with clinical sepsis admitted to 4 hospitals from 2013 to 2017 (only including patients’ first eligible ED encounter). Adjusted associations were measured using multivariable logistic regression, and secondary analyses employed measures of antibiotic timing (initiation within 1 or 3 hours, separate comparison of antibiotic exposure at each hour up to hour 6), alternative statistical methods to mitigate indication bias, and alternative outcomes (in-hospital, 30-day, and 90-day mortality).

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The median door-to-antibiotic time for the 10,811 patients included in the study was 166 minutes (interquartile range, 116-230 min). Patients who received antibiotics within 3 hours of arrival were older, had more comorbidities, were less likely to be women, had more physiologic derangement, and exhibited more organ failure. Of the 10,811 patients, 8% (n=887) died within 30 days, and 19% (n=2083) died within 1 year.

After adjustment, every increase in hour in door-to-antibiotic time was associated with a 10% (95% CI, 5%-14%) increase in the odds of 1-year mortality (P <.001), which translated to a 1.1% (95% CI, 0.7%-1.6%) increase in expected mortality for each additional hour of door-to-antibiotic time. This association remained linear when each 1-hour interval was independently compared with door-to-antibiotic time ≤1 hour and was similar for inpatient, 30-day, and 90-day mortality. One-year mortality was higher when door-to-antibiotic times were >3 hours compared with ≤3 hours (adjusted odds ratio, 1.27; 95% CI, 1.13-1.43) but not when times were >1 hour compared with ≤1 hour (adjusted odds ratio, 1.26, 95% CI, 0.98-1.62).

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Limitations to this study included possible underestimation between antibiotic delays and mortality, inclusion of patients with clinical rather than confirmed sepsis, and an inability to assess cause of death.

The investigators concluded that “innovative trial designs are needed to test methods to accelerate appropriate antibiotic initiation and determine whether these interventions improve patient-centered outcomes.”


Peltan ID, Brown SM, Bledsoe JR, et al. Emergency department door-to-antibiotic time and long-term mortality in sepsis [published online February 16, 2019]. CHEST. doi:10.1016/j.chest.2019.02.008