ED Door-to-Antibiotic Time and Long-term Mortality in Sepsis

Background: The impact of antibiotic timing on sepsis outcomes remains controversial due to conflicting results from previous studies. Objectives: This study investigated the association of door-to-antibiotic time with long-term mortality in ED patients with sepsis. Methods: This retrospective cohort study included nontrauma adult ED patients with clinical sepsis admitted to four hospitals from 2013 to 2017. Only patients’ first eligible encounter was included. Multivariable logistic regression was used to measure the adjusted association between door-to-antibiotic time and 1-year mortality. Secondary analyses used alternative antibiotic timing measures (antibiotic initiation within 1 or 3 h and separate comparison of antibiotic exposure at each hour up to hour 6), alternative outcomes (hospital, 30-day, and 90-day mortality), and alternative statistical methods to mitigate indication bias. Results: Among 10,811 eligible patients, median door-to-antibiotic time was 166 min (interquartile range, 115-230 min), and 1-year mortality was 19%. After adjustment, each additional hour from ED arrival to antibiotic initiation was associated with a 10% (95% CI, 5-14; P <.001) increased odds of 1-year mortality. The association remained linear when each 1-h interval of door-to-antibiotic time was independently compared with door-to-antibiotic time ≤ 1 h and was similar for hospital, 30-day, and 90-day mortality. Mortality at 1 year was higher when door-to-antibiotic times were > 3 h vs ≤ 3 h (adjusted OR, 1.27; 95% CI, 1.13-1.43) but not > 1 h vs ≤ 1 h (adjusted OR, 1.26; 95% CI, 0.98-1.62). Conclusions: Delays in ED antibiotic initiation time are associated with clinically important increases in long-term, risk-adjusted sepsis mortality.