In Reply: Timing of appropriate antibiotics in sepsis- how much does each hour matter?

To the Editor

We read the additional findings and data presented by Burnham et al with particular interest. (1,2) In their retrospective analysis of over 500 patients with sepsis, severe sepsis, and septic shock due to Enterobacteriaceae bacteremia, they found no significant association between timing of antibiotics and 30-day mortality. These findings are consistent with the data recently published in our meta-analysis, which also found no mortality benefit of administering antibiotics within 3 hours of emergency department triage or within 1 hour of severe sepsis or septic shock onset (3). A particular strength of the study by Burnham and colleagues is a far more homogenous study population, limited to a single, well defined microorganism. (2,3) This focus allows for the elimination of a major source of heterogeneity in patients in many clinical studies of the topic, namely variable and sometimes unclear sources of infection, which lends additional validity to their results. Given the total available evidence base to date, we agree that the potential but unclear benefits of early, broad spectrum antibiotic administration must be weighed versus the similarly important goal of antibiotic stewardship.