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

Whiles, Bristol B. BS1; Deis, Amanda S. MS1; Simpson, Steven Q. MD2

doi: 10.1097/CCM.0000000000002262
Clinical Investigations
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SDC

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.

1University of Kansas School of Medicine, Kansas City, Kansas.

2Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Kansas, Kansas City, Kansas.

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Ms. Whiles received funding from Alpha Omega Alpha Honor Medical Society Carolyn L. Kuckein Student Research Fellowship. Ms. Deis received a Clinical and Translational Science Awards (CTSA) Awards grant from National Center for Advancing Translational Science (NCATS) awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research TL1TR000120. Ms. Deis disclosed other support that she received support in the form of tuition while working on this project (TL1TR000120). Dr. Simpson received funding from Alpha Omega Alpha Honor Medical Society Carolyn L. Kuckein Student Research Fellowship and from CTSA grant from NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research #TL1TR000120.

For information regarding this article, E-mail: ssimpson3@kumc.edu

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