3 Key Takeaways
Plain English Summary- 01Core Finding
0-3h) and in-hospital mortality for each SEP-1 organ dysfunction criterion, alone and in combination: hypotension, elevated lactate, respiratory failure, renal dysfunction, hyperbilirubinemia, thrombocytopenia, and coagulopathy.
- 02Study Evidence
Tested in a ehr cohort study at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
What This Means for You
Mortality associations with antibiotics beyond 1 hour were most evident when sepsis time zero was defined by hypotension or lactate ≥4.0mmol/L, and with antibiotics beyond 3 hours when defined by acute respiratory failure. These findings could inform refinements to sepsis time zero definitions to better guide antibiotic urgency and performance measurement.
The Discovery
We analyzed adults with suspected infection using electronic health record data from 145 U.S. hospitals (2018-2023). We estimated associations between antibiotic timing (1-3 vs. 0-1h and 3-6 vs. 0-3h) and in-hospital mortality for each SEP-1 organ dysfunction criterion, alone and in combination: hypotension, elevated lactate, respiratory failure, renal dysfunction, hyperbilirubinemia, thrombocytopenia, and coagulopathy. We used inverse probability weighting to adjust for baseline and time-varying confounders. Among 1,849,729 encounters with suspected infection, 624,416 had ≥1 organ dysfunction and received antibiotics within 6h of time zero. Antibiotics at 1-3 vs. 0-1h were associated with higher mortality when time zero was defined by hypotension (aRR 1.07; 95% CI, 1.03-1.10) or lactate ≥4.0mmol/L (aRR 1.10; 1.05-1.15), but not for other dysfunctions alone or in combination. Among patients without hypotension or lactate ≥4.0mmol/L, antibiotics at 3-6 vs. 0-3h were only associated with higher mortality in patients with acute respiratory failure (aRR 1.11; 1.05-1.18).
How It Works, Simply
This pulmonology research focuses on airway remodeling & alveolar gas-exchange pathway. Researchers evaluated it using an eHR Cohort study at the real-world cohort stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
0-3h) and in-hospital mortality for each SEP-1 organ dysfunction criterion, alone and in combination: hypotension, elevated lactate, respiratory failure, renal dysfunction, hyperbilirubinemia, thrombocytopenia, and coagulopathy.
- 02Study Evidence
Tested in a ehr cohort study at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
Biological Mechanism & Study Design
Study Design & Cohort
EHR Cohort study
EHR Cohort study · Real-World Cohort
Biological Pathway & Modality
Airway remodeling & alveolar gas-exchange pathway
Intervention: Optimizing Sepsis Time Zero Definitions Through Associations between Antibiotic
Experimental Findings & Endpoints
We analyzed adults with suspected infection using electronic health record data from 145 U.S. hospitals (2018-2023).
We estimated associations between antibiotic timing (1-3 vs. 0-1h and 3-6 vs.
0-3h) and in-hospital mortality for each SEP-1 organ dysfunction criterion, alone and in combination: hypotension, elevated lactate, respiratory failure, renal dysfunction, hyperbilirubinemia, thrombocytopenia, and coagulopathy. We used inverse probability weighting to adjust for baseline and time-varying confounders.
Among 1,849,729 encounters with suspected infection, 624,416 had ≥1 organ dysfunction and received antibiotics within 6h of time zero. Antibiotics at 1-3 vs.
0-1h were associated with higher mortality when time zero was defined by hypotension (aRR 1.07; 95% CI, 1.03-1.10) or lactate ≥4.0mmol/L (aRR 1.10; 1.05-1.15), but not for other dysfunctions alone or in combination. Among patients without hypotension or lactate ≥4.0mmol/L, antibiotics at 3-6 vs.
0-3h were only associated with higher mortality in patients with acute respiratory failure (aRR 1.11; 1.05-1.18).
Clinical Translation & Practice Context
Mortality associations with antibiotics beyond 1 hour were most evident when sepsis time zero was defined by hypotension or lactate ≥4.0mmol/L, and with antibiotics beyond 3 hours when defined by acute respiratory failure.
These findings could inform refinements to sepsis time zero definitions to better guide antibiotic urgency and performance measurement.
The Bottom Line · Clinical Pearl
“Mortality associations with antibiotics beyond 1 hour were most evident when sepsis time zero was defined by hypotension or lactate ≥4.0mmol/L, and with antibiotics beyond 3 hours when defined by acute respiratory failure.”
Published in American Journal of Respiratory and Critical Care Medicine · Current Stage: Real-World Cohort