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


METHODS
This is a prospective multicenter study in three Dutch EDs. Patients were stratified into three categories of illness severity, as assessed by the predisposition, infection, response, and organ failure (PIRO) score: PIRO score 1 to 7, 8 to 14 and >14 points, reflected low, intermediate, and high illness severity, respectively. Consecutive hospitalized ED patients with a suspected infection who were treated with intravenous antibiotics were eligible to participate in the study. The primary outcome measure was the number of surviving days outside the hospital at day 28 which was used as an inverse measure of hospital length of stay (LOS). The secondary outcome measure was 28-day mortality, taking into account 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 three categories of illness severity.


RESULTS
Of the 1,168 included patients, 112 died (10%), while 85% and 95% received antibiotics within three and six hours, respectively. No association between time to antibiotics and surviving days outside the hospital or mortality was found. Only in PIRO group 1 to 7 was delayed administration of antibiotics (>3 hours) associated with an increase in surviving days outside the hospital at day 28 (hazard ratio: 1.46, 95% confidence interval: 1.05 to 2.02 after correction for potential confounders).


CONCLUSIONS
In ED patients with mild to severe sepsis who received antibiotics within six hours after ED presentation, a reduction in time to antibiotics was not found to be associated with an improvement in relevant clinical outcomes.
Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, the Netherlands. b.de_groot.SEH@lumc.nl.
Bas
B
de Groot
Rijnstate Hospital, Wagnerlaan 55, 6815 AD, Arnhem, the Netherlands. annemiekeansems@hotmail.com.
Annemieke
A
Ansems
Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, the Netherlands. d.h.gerling@umail.leidenuniv.nl.
Daan H
DH
Gerling
Rijnstate Hospital, Wagnerlaan 55, 6815 AD, Arnhem, the Netherlands. mail2@douwerijpsma.nl.
Douwe
D
Rijpsma
VU Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. p.vanamstel@vumc.nl.
Paul
P
van Amstel
VU Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. durklinzel@gmail.com.
Durk
D
Linzel
VU Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. pj.kostense@vumc.nl.
Piet J
PJ
Kostense
VU Medical Center, Boelelaan 1117, 1081 HV, Amsterdam, the Netherlands. m.jonker2@vumc.nl.
Marianne
M
Jonker
Leiden University Medical Center, Albinusdreef 2, 2300 RC, Leiden, the Netherlands. e.de_jonge@lumc.nl.
Evert
E
de Jonge
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D004636:Emergency Service, Hospital / Q000639:trends*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends; D063305:Organ Dysfunction Scores; D011446:Prospective Studies; D018805:Sepsis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D061665:Time-to-Treatment / Q000639:trends*; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents