Delays to Antibiotics in the Emergency Department and Risk of Mortality in Children With Sepsis

Roni D. Lane, Division of Pediatric Emergency Medicine, Department of Pediatrics, Primary Children's Hospital, University of Utah, Salt Lake City.
Troy Richardson, Children's Hospital Association, Lenexa, Kansas.
Halden F. Scott, Section of Emergency Medicine, Department of Pediatrics, University of Colorado School of Medicine, Aurora.
Raina M. Paul, Pediatric Emergency Medicine, Children's Hospital of Orange County, Orange, California.
Fran Balamuth, Division of Emergency Medicine, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia.
Matthew A. Eisenberg, Division of Emergency Medicine, Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Ruth Riggs, Children's Hospital Association, Lenexa, Kansas.
W Charles Huskins, Division of Pediatric Infectious Diseases, Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
Christopher M. Horvat, Department of Critical Care Medicine, UPMC, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
Grant E. Keeney, Department of Pediatric Emergency Medicine, Mary Bridge Children's Hospital, Tacoma, Washington.
Leslie A. Hueschen, Division of Emergency Medicine, Department of Pediatrics, Children's Mercy Hospital, University of Missouri-Kansas City, Kansas City.
Justin M. Lockwood, Section of Hospital Medicine, Department of Pediatrics, University of Colorado School of Medicine, Aurora.
Vishal Gunnala, Division of Critical Care Medicine, Phoenix Children's Hospital, Phoenix, Arizona.
Bryan P. McKee, Division of Critical Care Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio.
Nikhil Patankar, Pediatric Critical Care, Baptist St Anthony's Health System, Amarillo, Texas.
Venessa Lynn Pinto, Division of Pediatric Critical Care, Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
Amanda M. Sebring, Division of Pediatric Critical Care, Department of Pediatrics, Atrium Health Levine Children's, Charlotte, North Carolina.
Matthew P. Sharron, Division of Critical Care Medicine, Department of Pediatrics, Children's National Hospital, George Washington University School of Medicine, Washington, DC.
Jennifer Treseler, Program for Patient Safety and Quality, Boston Children's Hospital, Boston, Massachusetts.
Jennifer J. Wilkes, Division of Cancer and Blood Disorders, Department of Pediatrics, University of Washington School of Medicine, Seattle.
Jennifer K. Workman, Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City.

Document Type

Journal Article

Publication Date

6-3-2024

Journal

JAMA network open

Volume

7

Issue

6

DOI

10.1001/jamanetworkopen.2024.13955

Abstract

IMPORTANCE: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes. OBJECTIVE: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from 51 US children's hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024. EXPOSURE: The number of minutes from emergency department arrival to antibiotic administration. MAIN OUTCOMES AND MEASURES: The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome. RESULTS: A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes. CONCLUSIONS AND RELEVANCE: In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

Department

Pediatrics

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