Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis*. Crit Care Med. 2014 Nov; 42(11):2409-17.
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.
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.