Timing of antibiotics in septic patients: a prospective cohort study

Abstract

Objectives: To evaluate the effect of timing and appropriateness of antibiotics administration on mortality in patients diagnosed with sepsis according to the Sepsis-3 definition.

Methods: This prospective cohort study was conducted in patients diagnosed with sepsis according to the Sepsis-3 definition at the emergency department of Korea University Ansan Hospital from January 2016 to January 2019. The time to antibiotics was defined as the time in hours from emergency department arrival to the first antibiotic administration. Cox proportional hazards regression analysis was used to estimate the association between time to antibiotics and 7-, 14- and 28-day mortality.

Results: Of 482 patients enrolled onto this study, 203 (42.1%) of 482 and 312 (64.7%) of 482 were diagnosed with septic shock and high-grade infection respectively. The median time to receipt of antibiotic therapy was 115 minutes. Antibiotics were administered within 3 and 6 hours in 340 (70.4%) of 482 and 450 (93.2%) of 482 patients respectively. Initial appropriate empirical antibiotics were administered in 375 (77.8%) of 482 patients. The time to and appropriateness of the initial antibiotics were not associated with 7-, 14- and 28-day mortality in multivariate analysis. The Sequential Organ Failure Assessment (SOFA) score (adjusted hazard ratio (aHR) 1.229, 95% confidence interval (CI) 1.093-1.381, p 0.001) and initial lactate levels (aHR 1.128, 95% CI 1.034-1.230, p 0.007), Charlson comorbidity index (aHR 1.115, 95% CI 1.027-1.210, p 0.014), 2-hour lactate level (aHR 1.115, 95% CI 1.027-1.210, p 0.009) and SOFA score (aHR 1.077, 95% CI 1.013-1.144, p 0.018) affected 7-, 14- and 28-day mortality respectively. Subgroup analysis with septic shock, bacteraemia and high-grade infection did not affect mortality rates.

Conclusions: Time to receipt of antibiotics may not affect the prognosis of patients with sepsis if a rapid and well-trained resuscitation is combined with appropriate antibiotic administration within a reasonable time.

Keywords: Antibiotics; Appropriateness; Sepsis; Sepsis-3 definition; Timing.