The association between time to antibiotics and relevant clinical outcomes in emergency department patients with various stages of sepsis: a prospective multi-center study

Bas de Groot, Annemieke Ansems, Daan H Gerling, Douwe Rijpsma, Paul van Amstel, Durk Linzel, Piet J Kostense, Marianne Jonker, Evert de Jonge

In early sepsis stages, optimal treatment could contribute to prevention of progression to severe sepsis. Therefore, we investigated if there was an association between time to antibiotics and relevant clinical outcomes in hospitalized emergency department (ED) patients with mild to severe sepsis stages. Design. Prospective multi-centre study in 3 Dutch ED's. Patients were stratified in 3 categories of illness severity, as assessed by the predisposition, infection, response, organ failure (PIRO) score: PIRO score 1-7, 8-14 and >14 points reflected low, intermediate and high illness severity, respectively. Participents. Consecutive hospitalized ED patients with a suspected infection who were treated with intravenous antibiotics. Number of surviving days outside the hospital at day 28 was used as an inverse measure of hospital lengths of stay (LOS). Secondary outcome measure: 28-day mortality, taking into acccount the time to mortality. Multivariable Cox regression analysis was used to estimate the association between time to antibiotics and the primary and secondary outcome measures corrected for confounders, including appropriateness of antibiotics and initial ED resuscitation, in 3 categories of illness severity. Hundred twelve (10%) of 1168 included patients died, while 85% and 95% received antibiotics within 3 and 6 hours, respectively. No association between time to antibiotics and surviving days outside the hospital or mortality was found. Only in PIRO group 1-7 delayed administration of antibiotics (>3 hrs) was associated with an increase in surviving days outside the hospital at day 28 (HR 1.46, 95% CI 1.05-2.02 after correction for potential confounders). In ED patients with mild to severe sepsis who received antibiotics within 6 hours after ED presentation, a reduction in time to antibiotics was not found to be associated with an improvement in relevant clinical outcomes.