No Link Found Between Per-Hour Delay in Antibiotics and Mortality in Septic Shock

Sepsis, bacteria
Sepsis, bacteria
In this study, we found that early first antibiotic administration was associated with improved outcomes in ED patients with septic shock using propensity score analysis.

In septic shock, rapid antibiotic treatment with emergency department triage is generally associated with reduced in-hospital mortality, however, there is no linear association between every-hour delay of first antibiotic administration and mortality, according to study results published in the American Journal of Medicine.

Sepsis and septic shock are currently major causes of visits to the hospital emergency department. Current sepsis guidelines recommend starting antibiotics within 1 hour of triage in the emergency department, however, there is moderate quality of evidence regarding the association between the timing of antibiotic administration and outcomes in sepsis and septic shock. The objective of this study was to evaluate the association between the timing of antibiotic administration and in-hospital mortality in septic shock.

In this prospective multicenter observational study, researchers used data from the Korean Shock Society septic shock registry to identify patients with septic shock. Using data from the Korean Shock Society septic shock survey, researchers identified 2250 adult patients for inclusion in the study. Patients were divided into 4 groups by the interval from triage to first antibiotic administration: group 1 (≤1 hour; reference), group 2 (1-2 hours), group 3 (2-3 hours), and group 4 (>3 hours). The primary end point was in-hospital mortality, and subgroup analysis was performed on patients who received appropriate antibiotics, defined as “those having an identified organism with in vitro sensitivity to an administered antibiotic on body fluid culture.” The outcomes of all groups were compared following inverse probability of treatment weighting.

Results revealed that among the 2250 patients included in the study, in-hospital mortality was 22.8%. The median time to first antibiotic administration was 2.29 hours, and comparable between patients who survived and those who did not (2.22 vs 2.29 hours). Compared with group 1, the odds ratio for in-hospital mortality in groups 2, 3, and 4 were 1.248 (95% CI, 1.053-1.478; P =.011), 1.186 (95% CI, 0.999-1.408; P =.052), and 1.419 (95% CI, 1.203-1.675; P <.001), respectively. Multivariate analysis of the entire study cohort showed that group 4 had a significantly higher in-hospital mortality compared with group 1 (P=.006). Further analysis demonstrated that while participants in groups 2 and 4 had significantly higher in-hospital mortality rates, including when treated with appropriate antibiotics compared with group 1, the differences between group 1 and group 3 were insignificant.

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There were several limitations to this study. Researchers acknowledged, first, that this was a nonrandomized registry study. In addition, results may have been affected by the influence of unmeasured confounders, including differences in outcomes from each of the 10 participating hospitals. Data on the sepsis start-time were not available in the registry and, the timing of antibiotics may differ based on the sepsis screening strategy used in each hospital. Further, multivariable logistic regression excluded patients who died within 24 hours had no significant effect with regard to timing of antibiotics. Lastly, this study included only patients with septic shock, and did not examine the efficacy of antibiotic timing in patients with sepsis.

The study researchers concluded that rapid treatment with antibiotics may decrease in-hospital mortality in patients with septic shock, but no association exists between each hour delay of first antibiotic administration and in-hospital mortality.


Ko BS, Choi SH, Kang GH, et al. Time-to-antibiotics and the outcome of patients with septic shock: A propensity score analysis [published online October 14, 2019]. Am J Med. doi: 10.1016/j.amjmed.2019.09.012