The Timing of Early Antibiotics and Hospital Mortality in Sepsis

Abstract

Rationale: Prior sepsis studies evaluating antibiotic timing have shown mixed results.

Objectives: To evaluate the association between antibiotic timing and mortality among patients with sepsis receiving antibiotics within 6 hours of emergency department registration.

Methods: Retrospective study of 35,000 randomly selected inpatients with sepsis treated at 21 emergency departments between 2010 and 2013 in Northern California. The primary exposure was antibiotics given within 6 hours of emergency department registration. The primary outcome was adjusted in-hospital mortality. We used detailed physiologic data to quantify severity of illness within 1 hour of registration and logistic regression to estimate the odds of hospital mortality based on antibiotic timing and patient factors.

Measurements and main results: The median time to antibiotic administration was 2.1 hours (interquartile range, 1.4-3.1 h). The adjusted odds ratio for hospital mortality based on each hour of delay in antibiotics after registration was 1.09 (95% confidence interval [CI], 1.05-1.13) for each elapsed hour between registration and antibiotic administration. The increase in absolute mortality associated with an hour's delay in antibiotic administration was 0.3% (95% CI, 0.01-0.6%; P = 0.04) for sepsis, 0.4% (95% CI, 0.1-0.8%; P = 0.02) for severe sepsis, and 1.8% (95% CI, 0.8-3.0%; P = 0.001) for shock.

Conclusions: In a large, contemporary, and multicenter sample of patients with sepsis in the emergency department, hourly delays in antibiotic administration were associated with increased odds of hospital mortality even among patients who received antibiotics within 6 hours. The odds increased within each sepsis severity strata, and the increased odds of mortality were greatest in septic shock.

Keywords: antibacterial agents; sepsis; septic shock.

Figure 1.

Kernel density plot showing time to first antibiotic administration from emergency department registration. Distribution in the overall cohort is shown with a solid line, the septic shock cohort is shown in a dashed line, the severe sepsis cohort with a dotted line, and the sepsis cohort with a dashed-dotted line. ED = emergency department.

Figure 2.

Adjusted odds ratios for hospital mortality comparing patients within each hourly antibiotic administration group with the reference group of patients given antibiotics in <1 hour. The y-axis is on logarithmic scale and the error bars represent 95% confidence intervals.