Antibiotic Administration and Blood Culture Positivity in Severe Sepsis and Septic Shock

Sepsis is a significant cause health care expenditure and carries an extremely high rate of
morbidity and mortality if not treated appropriately. From 1979 to 2000, sepsis resulted in
over 10 million admissions to hospital in the United States with a mortality rate of 17.9 to
27.8 percent. In Canada, it is estimated that the incidence of sepsis from 2008-2009 was
103.3 per 100,000 per year.

Advances in the multifaceted management of sepsis in recent years have resulted in improved
clinical outcomes. However, the cornerstone of sepsis management relies on the prompt
administration of appropriate antibiotics. Current clinical practice suggests that antibiotic
administration can be delayed up to 45 minutes in order to obtain blood cultures, whose
results have a profound impact on the type and duration of antimicrobial therapy.
Unfortunately, this recommendation is based on very little evidence and the investigators
have found that potential life-saving treatment is often delayed in order to abide by it.
Furthermore, recent data suggest that mortality could be increased by approximately 5% by
delaying antibiotic administration for that time period.

The investigators therefore wish to organize a prospective, multi-centre trial in order to
identify the effect of antibiotic administration on blood culture positivity in patients
presenting with severe sepsis or septic shock. Other objectives will be to elucidate which
patient factors, including age, co-morbid conditions and clinical presentation, as well as
antibiotic choice will affect blood culture results.

This study will be conducted in the emergency departments at St. Paul's Hospital (SPH),
Vancouver General Hospital (VGH), Lion's Gate Hospital (LGH), Surrey Memorial Hospital,
Montreal General Hospital (MGH), Royal Victoria Hospital (RVH) and Maricopa Integrated Health
System. Patients identified for the aforementioned conditions will be treated as per routine
hospital protocol. If the patient is deemed eligible for the study, a second set of blood of
blood cultures will subsequently be drawn ideally between 30 and 60 minutes after the
administration of antibiotic therapy. Subject demographic data will be collected pertaining
to age, comorbid immunocompromised conditions, vital signs, laboratory tests pertaining to
end organ dysfunction, suspected source of sepsis, the type antibiotics administered and the
timing of antimicrobial administration with respect to the second set of blood cultures
taken.

Our hypothesis is that blood culture positivity in patients presenting with severe sepsis and
septic shock will not be altered significantly by antibiotic therapy. If so, our study would
strongly argue against delaying life-saving therapy and would thus greatly improve patient
care in our local emergency rooms. If incorrect, our study would be the first to demonstrate
the benefit of obtaining blood cultures before antibiotic therapy and would strengthen
current recommendations.