• Sarah A Sterling, W Ryan Miller, Jason Pryor, Michael A Puskarich, and Alan E Jones.
• All authors: Department of Emergency Medicine, University of Mississippi School of Medicine, Jackson, MS.
• Crit. Care Med. 2015 Sep 1; 43 (9): 1907-15.

ObjectivesWe sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock.Data SourcesA comprehensive search criteria was performed using a predefined protocol.Study SelectionInclusion Criteriaadult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to emergency department triage and/or shock recognition, and mortality.Exclusion Criteriaimmunosuppressed populations, review article, editorial, or nonhuman studies.Data ExtractionTwo reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of emergency department triage and 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds ratios were calculated using a random effect model. The primary outcome was mortality.Data SynthesisA total of 1,123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from emergency department triage. Patients who received antibiotics more than 3 hours after emergency department triage (< 3 hr reference) had a pooled odds ratio for mortality of 1.16 (0.92-1.46; p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hr reference) had a pooled odds ratio for mortality of 1.46 (0.89-2.40; p = 0.13). There was no increased mortality in the pooled odds ratios for each hourly delay from less than 1 to more than 5 hours in antibiotic administration from severe sepsis/shock recognition.ConclusionUsing the available pooled data, we found no significant mortality benefit of administering antibiotics within 3 hours of emergency department triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence.

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