Evaluating potential modifications to the Centers for Disease Control and Prevention’s Adult Sepsis Event definition: impact on sepsis incidence, outcomes, and clinical validity

Objective: To evaluate potential modifications to the Centers for Disease Control and Prevention (CDC)’s Adult Sepsis Event (ASE) definition aimed at mitigating variable blood culturing practices, better-capturing cases where timely care may have prevented deterioration, and improving clinical credibility. Design: Retrospective observational study Setting: 5 US hospitals Patients: Hospitalized adults, 2015–2022 Methods: We assessed the impact of potential ASE modifications on community-onset sepsis incidence and mortality and reviewed 280 charts to assess positive predictive value (PPV) for clinical sepsis. Results: Among 1,101,252 hospitalized adults, 51,712 (4.7%) met community-onset ASE criteria (16.1% mortality). Expanding infection criteria to include present-on-admission infection codes when blood cultures were not drawn, non-blood clinical cultures, and discharge alive on antibiotic day three increased incidence by 15.0%, 12.2%, and 4.9%, respectively; all led to mild decreases in mortality rates. Expanding organ dysfunction criteria to include hypotension increased ASE incidence by 32.3% and decreased mortality by 18.5%. Broadening respiratory failure criteria to include noninvasive ventilation and high-flow oxygen had minimal impact. On chart review, original ASE criteria had 80% PPV for clinical sepsis. PPV was similar when identifying infection using present-on-admission infection codes instead of blood cultures and when including patients discharged alive on antibiotic day three. PPV decreased to 50% when using non-blood clinical cultures to identify infection, 17% when using single hypotension values alone to indicate organ dysfunction, and 30% when all ASE components occurred exactly 2 days vs within +/-1 day from the blood culture day. Conclusions: Our findings inform modifications to ASE to optimize its utility for national epidemiologic monitoring and quality measurement.