title: Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis.
abstract: OBJECTIVE
  Delayed 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.
  
  
  METHODS
  Retrospective observational study.
  
  
  METHODS
  PICU at an academic medical center.
  
  
  METHODS
  One hundred thirty patients treated for severe sepsis or septic shock.
  
  
  METHODS
  None.
  
  
  RESULTS
  We 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).
  
  
  CONCLUSIONS
  Delayed antimicrobial therapy was an independent risk factor for mortality and prolonged organ dysfunction in pediatric sepsis.
authors.affiliation: 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.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Weiss
authors.forename: Julie C
authors.initials: JC
authors.lastname: Fitzgerald
authors.forename: Fran
authors.initials: F
authors.lastname: Balamuth
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Alpern
authors.forename: Jane
authors.initials: J
authors.lastname: Lavelle
authors.forename: Marianne
authors.initials: M
authors.lastname: Chilutti
authors.forename: Robert
authors.initials: R
authors.lastname: Grundmeier
authors.forename: Vinay M
authors.initials: VM
authors.lastname: Nadkarni
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
mesh_terms: D000046:Academic Medical Centers; D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016638:Critical Illness / Q000401:mortality / Q000628:therapy; D004334:Drug Administration Schedule; D005260:Female; D017052:Hospital Mortality; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D015278:Intensive Care Units, Pediatric; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000401:mortality*; D015999:Multivariate Analysis; D015143:Philadelphia; D012189:Retrospective Studies; D018570:Risk Assessment; D018805:Sepsis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D012772:Shock, Septic / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality; D015996:Survival Rate; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents