Derivation of a clinical-based model to detect invasive bacterial infections in febrile infants

Abstract

Background: Febrile infants are at risk for invasive bacterial infections (IBIs) (i.e., bacteremia and bacterial meningitis), which, when undiagnosed, may have devastating consequences. Current IBI predictive models rely on serum biomarkers, which may not provide timely results and may be difficult to obtain in low-resource settings.

Objective: The aim of this study was to derive a clinical-based IBI predictive model for febrile infants.

Designs, setting, and participants: This is a cross-sectional study of infants brought to two pediatric emergency departments from January 2011 to December 2018. Inclusion criteria were age 0-90 days, temperature ≥38°C, and documented gestational age, fever duration, and illness duration.

Main outcome and measures: To detect IBIs, we used regression and ensemble machine learning models and evidence-based predictors (i.e., sex, age, chronic medical condition, gestational age, appearance, maximum temperature, fever duration, illness duration, cough status, and urinary tract inflammation). We up-weighted infants with IBIs 8-fold and used 10-fold cross-validation to avoid overfitting. We calculated the area under the receiver operating characteristic curve (AUC), prioritizing a high sensitivity to identify the optimal cut-point to estimate sensitivity and specificity.

Results: Of 2311 febrile infants, 39 had an IBI (1.7%); the median age was 54 days (interquartile range: 35-71). The AUC was 0.819 (95% confidence interval: 0.762, 0.868). The predictive model achieved a sensitivity of 0.974 (0.800, 1.00) and a specificity of 0.530 (0.484, 0.575). Findings suggest that a clinical-based model can detect IBIs in febrile infants, performing similarly to serum biomarker-based models. This model may improve health equity by enabling clinicians to estimate IBI risk in any setting. Future studies should prospectively validate findings across multiple sites and investigate performance by age.