Severe sepsis and septic shock remain a major cause of
emergency departmentvisits and ICU admissions
and are associated with significant morbidity, mortality,
and healthcare costs. Previous studies have suggested
improved outcomes with the implementation of a structured
resuscitation, focusing largely on IV fluid resuscitation, timely
broad-spectrum antibiotics, and vasopressor therapy.
Although some authors have suggested the primacy of timely
antibiotics administration for improved mortality in severe
sepsis and septic shock, previously published research
evaluating the association of the time to antibiotic administration on outcomes has produced disparate results.
In 2006, Kumar reported a 7.6% increase in mortal-ity in patients with sepsis for each hourly delay after the onset of
shock. Although subsequent studies have failed to demonstrate
such substantial results, several studies have reported increased
mortality associated with delays in antibiotic administration either
from shock recognition or time from ED triage. Other
studies have not demonstrated any increase in mortality with delay
of antibiotic administration based on triage time. The most recent Surviving Sepsis Campaign guidelines include specific recommendations regarding the timing of antibiotics: “The administration of effective IV antimicrobials within the first hour of recognition of septic shock
and severe sepsis without septic shock
should be the goal of therapy”. Additionally, the SSC
recommends a “sepsis bundle,” which requires administra-tion of broadspectrum antibiotics within 3 hours from ED
triage. The authors of the SSC guidelines note that achiev-ing these goals may not be operationally feasible in some
cases and acknowledge that previous research has shown
that compliance with guidelines regarding antibiotic administration frequently is not achieved. Despite these
limitations, time to antibiotics administration has gained
increasing focus as a potential metric for the quality of care
of patients with severe sepsis and septic shock. To our knowledge, no previous study has pooled the available data to evaluate the impact of time to antibiotics on sepsis outcomes. Our objective was to perform a systematic review
of the published literature and to meta-analyze the available
data on the association between the timing of antibiotics and
mortality in severe sepsis and septic shock.