Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis

Scott L. Weiss, Julie C. Fitzgerald, Fran Balamuth, Elizabeth R. Alpern, Jane Lavelle, Marianne Chilutti, Robert Grundmeier, Vinay M. Nadkarni, Neal J. Thomas

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Objectives: 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. Design: Retrospective observational study. Setting: PICU at an academic medical center. Patients: One hundred thirty patients treated for severe sepsis or septic shock. Interventions: None. Measurements and Main 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.

Original languageEnglish (US)
Pages (from-to)2409-2417
Number of pages9
JournalCritical care medicine
Volume42
Issue number11
DOIs
StatePublished - Jan 1 2014

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Sepsis
Pediatrics
Mortality
Therapeutics
Septic Shock
Odds Ratio
Propensity Score
Mechanical Ventilators
Observational Studies
Length of Stay
Retrospective Studies

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

Weiss, Scott L. ; Fitzgerald, Julie C. ; Balamuth, Fran ; Alpern, Elizabeth R. ; Lavelle, Jane ; Chilutti, Marianne ; Grundmeier, Robert ; Nadkarni, Vinay M. ; Thomas, Neal J. / Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. In: Critical care medicine. 2014 ; Vol. 42, No. 11. pp. 2409-2417.
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title = "Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis",
abstract = "Objectives: 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. Design: Retrospective observational study. Setting: PICU at an academic medical center. Patients: One hundred thirty patients treated for severe sepsis or septic shock. Interventions: None. Measurements and Main 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.",
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Weiss, SL, Fitzgerald, JC, Balamuth, F, Alpern, ER, Lavelle, J, Chilutti, M, Grundmeier, R, Nadkarni, VM & Thomas, NJ 2014, 'Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis', Critical care medicine, vol. 42, no. 11, pp. 2409-2417. https://doi.org/10.1097/CCM.0000000000000509

Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. / Weiss, Scott L.; Fitzgerald, Julie C.; Balamuth, Fran; Alpern, Elizabeth R.; Lavelle, Jane; Chilutti, Marianne; Grundmeier, Robert; Nadkarni, Vinay M.; Thomas, Neal J.

In: Critical care medicine, Vol. 42, No. 11, 01.01.2014, p. 2409-2417.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis

AU - Weiss, Scott L.

AU - Fitzgerald, Julie C.

AU - Balamuth, Fran

AU - Alpern, Elizabeth R.

AU - Lavelle, Jane

AU - Chilutti, Marianne

AU - Grundmeier, Robert

AU - Nadkarni, Vinay M.

AU - Thomas, Neal J.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Objectives: 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. Design: Retrospective observational study. Setting: PICU at an academic medical center. Patients: One hundred thirty patients treated for severe sepsis or septic shock. Interventions: None. Measurements and Main 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.

AB - Objectives: 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. Design: Retrospective observational study. Setting: PICU at an academic medical center. Patients: One hundred thirty patients treated for severe sepsis or septic shock. Interventions: None. Measurements and Main 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.

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