To evaluate whether delay between the first and second antibiotic administered for suspected sepsis is associated with hospital mortality.

Retrospective cohort.

Twelve hospitals in Southeastern United States from 2014 to 2017.

25,717 adults with suspected sepsis presenting to 12 Emergency Departments who received at least two antibiotics within 12 h.

The primary exposure was first-to-second antibiotic delay >1 h. We used generalized linear mixed models to model the association between first-to-second antibiotic delay and hospital death in the overall cohort, and in subgroups of patients with and without septic shock. Overall, 13,852 (54%) patients had first-to-second antibiotic delay >1 h and 1666 (7%) died. Adjusting for other risk factors, first-to-second antibiotic delay was associated with increased risk of hospital death in the subgroup of patients with septic shock (OR 1.34; 95% CI: 1.05–1.70), but not among patients without shock (OR 0.99; 95% CI: 0.88–1.12) or in the overall cohort (OR 1.08; 95% CI: 0.97–1.20).

First-to-second antibiotic delay of greater than one hour was associated with an increased risk of hospital death among patients meeting criteria for septic shock but not all patients with suspected sepsis. Tracking and improving first-to-second antibiotic delays may be considered in septic shock.