title: Association of Delayed Antimicrobial Therapy with One-Year Mortality in Pediatric Sepsis.
abstract: Delayed antimicrobial therapy in sepsis is associated with increased hospital mortality, but the impact of antimicrobial timing on long-term outcomes is unknown. We tested the hypothesis that hourly delays to antimicrobial therapy are associated with 1-year mortality in pediatric severe sepsis.
  
  
  
  Retrospective observational study.
  
  
  
  Quaternary academic pediatric intensive care unit (PICU) from February 1, 2012 to June 30, 2013.
  
  
  
  One hundred sixty patients aged ≤21 years treated for severe sepsis.
  
  
  
  None.
  
  
  
  We tested the association of hourly delays from sepsis recognition to antimicrobial administration with 1-year mortality using multivariable Cox and logistic regression. Overall 1-year mortality was 24% (39 patients), of whom 46% died after index PICU discharge. Median time from sepsis recognition to antimicrobial therapy was 137 min (IQR 65-287). After adjusting for severity of illness and comorbid conditions, hourly delays up to 3 h were not associated with 1-year mortality. However, increased 1-year mortality was evident in patients who received antimicrobials ≤1 h (aOR 3.8, 95% CI 1.2, 11.7) or >3 h (aOR 3.5, 95% CI 1.3, 9.8) compared with patients who received antimicrobials within 1 to 3 h from sepsis recognition. For the subset of patients who survived index PICU admission, antimicrobial therapy ≤1 h was also associated with increased 1-year mortality (aOR 5.5, 95% CI 1.1, 27.4), while antimicrobial therapy >3 h was not associated with 1-year mortality (aOR 2.2, 95% CI 0.5, 11.0).
  
  
  
  Hourly delays to antimicrobial therapy, up to 3 h, were not associated with 1-year mortality in pediatric severe sepsis in this study. The finding that antimicrobial therapy ≤1 h from sepsis recognition was associated with increased 1-year mortality should be regarded as hypothesis-generating for future studies.
authors.affiliation: *Division of Critical Care Medicine, Department of Anesthesiology and Critical Care, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania †Division of Emergency Medicine, Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania ‡McCourt School of Public Policy and Department of Government, Georgetown University, Washington DC §Division of Emergency Medicine, Department of Pediatrics, Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois ||Department of Biomedical and Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania ¶Department of Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania #Division of Pediatric Critical Care Medicine, Penn State Hershey Children's Hospital, Penn State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Moonjoo
authors.initials: M
authors.lastname: Han
authors.forename: Julie C
authors.initials: JC
authors.lastname: Fitzgerald
authors.forename: Fran
authors.initials: F
authors.lastname: Balamuth
authors.forename: Luke
authors.initials: L
authors.lastname: Keele
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 W
authors.initials: RW
authors.lastname: Grundmeier
authors.forename: Vinay M
authors.initials: VM
authors.lastname: Nadkarni
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
authors.forename: Scott L
authors.initials: SL
authors.lastname: Weiss
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007223:Infant; D007362:Intensive Care Units / Q000706:statistics & numerical data; D015278:Intensive Care Units, Pediatric; D016015:Logistic Models; D008297:Male; D012189:Retrospective Studies; D018805:Sepsis / Q000188:drug therapy / Q000401:mortality*; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality*
chemical_list: D000900:Anti-Bacterial Agents