Is Time to Antibiotics a Good Metric for Sepsis?


  • Optimal antibiotic timing remains an actively debated topic.
  • Sepsis is an extremely heterogeneous syndrome, therefore, with which characteristics do earlier antibiotic administration improve outcomes?
  • A more nuanced process may be needed, rather than simply time to antibiotics.


  • Sepsis is an extremely heterogeneous syndrome with a multitude of potential presentations.
  • Recently attention has focused on the timeframe of antibiotic administration to improve sepsis-related mortality. Controversy exists regarding:
    • The correct timeframe that antibiotic administration impacts outcomes.
    • Differences between antibiotic order time vs administration time.
    • Differences in treatment and outcomes within specific subgroups.
  • Can specific factors determine which patients will benefit from early antibiotic administration?


  • The most recent contribution to this topic was a retrospective review of 18,315 patients within a 7 hospital system from 2010 to 2016.
  • 2 Major findings:
    • Antibiotic administration in patients with sepsis is characterized as a

      “J-Shaped Curve”

      • Antibiotics administered within the first hour had higher unadjusted mortality and prolonged length of stay (LOS).

      • LOS & mortality decreased over the next 3 hours

      • Then increased after 4 hours

Patients receiving antibiotics immediately upon arrival had higher mortality which was not achieved again until antibiotic administration equivalent to 8 hours after admission.

  • When risk adjusted, earlier time to antibiotics was associated with better outcomes in all patients.
    • Including patients with or without SIRS and organ dysfunction.
    • Mortality and LOS decreased if antibiotics were administered prior to 2.5 hours after admission.
      • LOS & mortality increased in all patients with antibiotics administered after 2.5 hours.
  • Predictors of antibiotic timing fall into similar categories for patients with and without sepsis.
    • In both groups of patients, lower antibiotic administration time is associated with improved outcomes if administered before 2.5 hours.
    • Predictors of antibiotic-associated outcomes fell into similar categories for patients with and without sepsis.
      • Temperature
      • Respiratory Rate
      • Diastolic Blood Pressure
      • RBC distribution width
  • Timeliness of antibiotic administration is not random, but influenced by patient characteristics.


  • Patients receiving antibiotics earlier on admission were more likely to have higher illness acuity (shock, tachypnea, fever, elevated lactate).
  • Patients receiving antibiotics later on admission were more likely to have a chronic illness (Liver dysfunction, Chronic Renal Disease, malignancy).
  • Replacing Time-To-Antibiotic metric with a risk-adjustment to account for diverse patient presentations independent of sepsis may be a better metric.

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Erkan Hassan is the Co-Founder & Chief Clinical Officer of Sepsis Program Optimization where he designs & oversees the implementation of solutions to optimize sepsis programs.

To discuss your organization’s Barriers of Effective Sepsis Care, contact Erkan by phone (844) 4SEPSIS (844-473-7747), email (, or video chat.