Clinicians' decision thresholds for initiating antibiotics in patients with suspected sepsis have not been quantified. We aimed to define an average threshold of infection likelihood at which clinicians initiate antibiotics when treating a patient with suspected infection and to evaluate the influence of severity of illness and clinician-related factors on the threshold. This was a prospective survey of 153 clinicians responding to 8 clinical vignettes constructed from real-world data from 3 health care systems in the United States. We treated each hour in the vignette as a decision to treat or not treat with antibiotics and assigned an infection probability to each hour using a previously developed infection prediction model. We then estimated decision thresholds using regression models based on the timing of antibiotic initiation. We compared thresholds across categories of severity of illness and clinician-related factors. Overall, the treatment threshold occurred at a 69% probability of infection, but the threshold varied significantly across severity of illness categories-when patients had high severity of illness, the treatment threshold occurred at a 55% probability of infection; when patients had intermediate severity, the threshold for antibiotic initiation occurred at an infection probability of 69%, and the threshold was 84% when patients had low severity of illness (P < 0.001 for group differences). Thresholds differed significantly across specialty, highest among infectious disease and lowest among emergency medicine clinicians and across years of experience, decreasing with increasing years of experience. The threshold infection probability above which physicians choose to initiate antibiotics in suspected sepsis depends on illness severity as well as clinician factors. Incorporating these context-dependent thresholds into discriminating and well-calibrated models will inform the development of future sepsis clinical decision support systems. Clinician-related differences in treatment thresholds suggests potential unwarranted variation and opportunities for performance improvement. Decision making about antibiotic initiation in suspected sepsis occurs under uncertainty, and little is known about clinicians' thresholds for treatment.In this prospective study, 153 clinicians from 3 health care systems reviewed 8 real-world clinical vignettes representing patients with sepsis and indicated the time that they would initiate antibiotics.Using a model-based approach, we estimated decision thresholds and found that thresholds differed significantly across illness severity categories and by clinician specialty and years of experience.
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