• Scott L Weiss, Julie C Fitzgerald, Fran Balamuth, Elizabeth R Alpern, Jane Lavelle, Marianne Chilutti, Robert Grundmeier, Vinay M Nadkarni, and Neal J Thomas.
• 1Division of Critical Care Medicine, Department of Anesthesia and Critical Care, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 2Division of Emergency Medicine, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 3Division of Emergency Medicine, Department of Pediatrics, Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL. 4The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA. 5Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 6Division of Pediatric Critical Care Medicine, Penn State Hershey Children's Hospital, Penn State University College of Medicine, Hershey, PA.
• Crit. Care Med. 2014 Nov 1; 42 (11): 2409-17.

ObjectivesDelayed antimicrobials are associated with poor outcomes in adult sepsis, but data relating antimicrobial timing to mortality and organ dysfunction in pediatric sepsis are limited. We sought to determine the impact of antimicrobial timing on mortality and organ dysfunction in pediatric patients with severe sepsis or septic shock.DesignRetrospective observational study.SettingPICU at an academic medical center.PatientsOne hundred thirty patients treated for severe sepsis or septic shock.InterventionsNone.Measurements And Main ResultsWe determined if hourly delays from sepsis recognition to initial and first appropriate antimicrobial administration were associated with PICU mortality (primary outcome); ventilator-free, vasoactive-free, and organ failure-free days; and length of stay. Median time from sepsis recognition to initial antimicrobial administration was 140 minutes (interquartile range, 74-277 min) and to first appropriate antimicrobial was 177 minutes (90-550 min). An escalating risk of mortality was observed with each hour delay from sepsis recognition to antimicrobial administration, although this did not achieve significance until 3 hours. For patients with more than 3-hour delay to initial and first appropriate antimicrobials, the odds ratio for PICU mortality was 3.92 (95% CI, 1.27-12.06) and 3.59 (95% CI, 1.09-11.76), respectively. These associations persisted after adjustment for individual confounders and a propensity score analysis. After controlling for severity of illness, the odds ratio for PICU mortality increased to 4.84 (95% CI, 1.45-16.2) and 4.92 (95% CI, 1.30-18.58) for more than 3-hour delay to initial and first appropriate antimicrobials, respectively. Initial antimicrobial administration more than 3 hours was also associated with fewer organ failure-free days (16 [interquartile range, 1-23] vs 20 [interquartile range, 6-26]; p = 0.04).ConclusionsDelayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.

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