Association between timing and adequacy of antibiotics and adverse outcomes in patients with sepsis and septic shock : a multicentre retrospective cohort study

Objectives: To investigate the association between the timing and adequacy of antibiotics administered to patients presenting with culture-positive sepsis and septic shock to the ED and in-hospital mortality and/or intensive care unit (ICU) admission. Methods: Multicentre retrospective cohort study of ED presentations at four metropolitan hospitals in Sydney, Australia between January 2017 and November 2019. Encounters for patients aged ≥16 years meeting specified criteria for sepsis or septic shock with antibiotic administration within the first 6 h of presentation were included. Results: Of 7611 encounters included in the study, 2328 (31%) were culture positive, and 2228 (29%) met the criteria for septic shock. In culture-positive sepsis encounters, partial or inadequate antibiotic coverage was associated with higher risk of death or ICU admission (adjusted odds ratio [AOR] 1.50, 95% confidence interval [CI] 1.04–2.06 and 1.95, 95% CI 1.28–2.99, respectively). This effect was not significant in septic shock encounters (AOR 1.10, 95% CI 0.64–1.88) with partial coverage and (AOR 1.63, 95% CI 0.81–3.3) inadequate coverage. Time to antibiotics was not significantly associated with the risk of mortality/ICU admission. This inference remained the same when analysis was restricted to cases with adequate antibiotic coverage. Conclusions: In a large multicentre sample of patients with culture-positive sepsis, inadequacy of antibiotics was associated with higher risk of in-hospital mortality or ICU admission.