How early do antibiotics have to be to impact mortality in severe sepsis? A prospective, observational study from an emergency department.

The objective of this study was to assess the promptness of antibiotic administration to patients presenting with sepsis and the effects on survival and length of hospitalization. Consecutive, adult patients presenting with Systemic Inflammatory Response Syndrome (SIRS) to the emergency department of the Aga Khan University hospital were enrolled in a prospective, observational study over a period of 4 months. Univariate, multivariate regression modeling and one-way ANOVA were used to examine the effects of various variables on survival and for significant differences between timing of antibiotic administration and survival, two-sided p values < 0.05 were considered significant. One hundred and eleven patients were enrolled. Severe sepsis was present in 52% patients; the most frequent organism isolated was Salmonella typhi (18%). Overall mortality was 35.1%. One hundred (90.1%) patients received intravenous antibiotics in the Emergency room; average time from triage to actual administration was 2.48 +/- 1.86 hours. The timing of antibiotic administration was significantly associated with survival (F statistic 2.17, p = 0.003). Using a Cox Regression model, we were able to demonstrate that survival dropped acutely with every hourly delay in antibiotic administration. On multivariate analysis, use of vasopressors (adjusted OR 23.89, 95% CI 2.16,263, p = 0.01) and Escherichia coli sepsis (adjusted OR 6.22, 95% CI 1.21,32, p = 0.03) were adversely related with mortality. We demonstrated that in the population presenting to our emergency room, each hourly delay in antibiotic administration was associated with an increase in mortality.