Discriminating Bacterial from Nonbacterial Lower Respiratory Tract Infection within Clinical Subgroups of Hospitalized Adults.

Falsey, Ann R; Peterson, Derick R; Baran, Andrea M; Walsh, Edward E; Bhattacharya, Soumyaroop; Branche, Angela R; Croft, Daniel P; Mariani, Thomas J · J Infect Dis · 2026

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Abstract

We previously identified a blood-based 4-gene signature that accurately discriminates bacterial from nonbacterial acute respiratory infection (ARI) in 504 hospitalized adults (AUC = 0.90). Here we evaluate how well this global signature performs within subgroups of patients based on underlying lung disease or presence of pneumonia, comparing it to newly developed subgroup-specific signatures assessing whether performance is improved by tailoring unique gene signatures to homogeneous subgroups. Our global gene signature strongly discriminated bacterial from nonbacterial ARI within every clinical subgroup including pneumonia (AUC = 0.77-0.94), and outperformed every subgroup-specific signature (AUC = 0.57-0.90), suggesting broad applicability in adults with ARI.