Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients

Objectives: To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock. Design: Retrospective cohort. Setting: Six hundred fifty-six bed urban academic medical center. Patients: Emergency department patients greater than or equal to 18 years old with severe sepsis and/or septic shock and antimicrobial administration within 24 hours. Patients with shock on presentation were excluded. Interventions: Not available. Measurements and Main Results: We identified 3,929 severe sepsis patients, with overall mortality 12.8%. Nine hundred eighty-four patients (25.0%) progressed to septic shock. The median time to antimicrobial was 3.77 hours (interquartile range = 1.96–6.42) in those who progressed versus 2.76 hours (interquartile range = 1.60–4.82) in those who did not (p < 0.001). Multivariate logistic regression demonstrated that male sex (odds ratio = 1.18; 95% CI, 1.01–1.36), Charlson Comorbidity Index (odds ratio = 1.18; 95% CI, 1.11–1.27), number of infections (odds ratio = 1.05; 95% CI, 1.02–1.08), and time to first antimicrobial (odds ratio = 1.08; 95% CI, 1.06–1.10) were associated with progression. Each hour until initial antimicrobial administration was associated with a 8.0% increase in progression to septic shock. Additionally, time to broad-spectrum antimicrobial was associated with progression (odds ratio = 1.06; 95% CI, 1.05–1.08). Time to initial antimicrobial was also associated with in-hospital mortality (odds ratio = 1.05; 95% CI, 1.03–1.07). Conclusions: This study emphasizes the importance of early, broad-spectrum antimicrobial administration in severe sepsis patients admitted through the emergency department, as longer time to initial antimicrobial administration is associated with increased progression of severe sepsis to septic shock and increased mortality.

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