Objectives: There is mounting evidence that delays in appropriate antimicrobial administration are responsible for preventable deaths in patients with sepsis. Herein, we examine the association between potentially modifiable antimicrobial administration delays, measured by the time from the first order to the first administration (antimicrobial lead time), and death among people who present with new onset of sepsis.
Design: Observational cohort and case-control study.
Setting: The emergency department of an academic, tertiary referral center during a 3.5-year period.
Patients: Adult patients with new onset of sepsis or septic shock.
Interventions: None.
Measurements and main results: We enrolled 4,429 consecutive patients who presented to the emergency department with a new diagnosis of sepsis. We defined 0-1 hour as the gold standard antimicrobial lead time for comparison. Fifty percent of patients had an antimicrobial lead time of more than 1.3 hours. For an antimicrobial lead time of 1-2 hours, the adjusted odds ratio of death at 28 days was 1.28 (95% CI, 1.07-1.54; p = 0.007); for an antimicrobial lead time of 2-3 hours was 1.07 (95% CI, 0.85-1.36; p = 0.6); for an antimicrobial lead time of 3-6 hours was 1.57 (95% CI, 1.26-1.95; p < 0.001); for an antimicrobial lead time of 6-12 hours was 1.36 (95% CI, 0.99-1.86; p = 0.06); and for an antimicrobial lead time of more than 12 hours was 1.85 (95% CI, 1.29-2.65; p = 0.001).
Conclusions: Delays in the first antimicrobial execution, after the initial clinician assessment and first antimicrobial order, are frequent and detrimental. Biases inherent to the retrospective nature of the study apply. Known biologic mechanisms support these findings, which also demonstrate a dose-response effect. In contrast to the elusive nature of sepsis onset and sepsis onset recognition, antimicrobial lead time is an objective, measurable, and modifiable process.