Background: Febrile infants ≤90 days are at high risk of serious bacterial infections, but prompt differentiation between viral and bacterial infections remains a challenge. Host gene expression signatures, particularly those involving the type I interferon (IFN) pathway, show promise as diagnostic tools. This study evaluates the ability of IFN signature to differentiate bacterial from viral infections in this population. Methods: This is a prospective, single-center study. Infants ≤90 days were enrolled. All patients underwent complete blood count, CRP, PCT, and IFN signature, assessed by analyzing the expression of six interferon-stimulated genes. Based on routine investigations, patients were divided into bacterial (BI, n = 8) and non-bacterial infection (non-BI, n = 39) and healthy controls (HC, n = 3). Regression analysis was used to determine the variable’s predictive correlation. Results: Forty-seven febrile infants were enrolled. IFN signature resulted significantly elevated in non-BI compared to BI (p < 0.001) and HC (p = 0.008), even within 12 h of fever onset. IFN demonstrated the highest AUC for predicting BI. Combining IFN with CRP or PCT yielded the most robust predictive models (AUC = 0.99 and 0.98). Conclusions: IFN signature resulted as a promising, reliable predictor of BI versus non-BI in febrile infants. This novel biomarker, combined with others, could improve the management of febrile infants reducing unnecessary antibiotics and hospitalizations. Impact: This is the first study to focus on the IFN signature in febrile infants under 90 days old, adding novel insights into the potential of host immune responses as diagnostic biomarkers. This study demonstrates that the peripheral blood interferon signature, specifically the expression of six IFN-stimulated genes, can distinguish bacterial from non-bacterial infections in febrile infants aged 90 days or younger in the very first hours of fever. The IFN score, when combined with traditional inflammatory markers, offers high sensitivity and specificity, making it a potential diagnostic tool for optimizing treatment and reducing unnecessary interventions.
Early diagnosis of serious bacterial infection in febrile infants using type I interferon signature
Fueri E.;Bustaffa M.;Serafino F.;Piccotti E.;Papa R.;Volpi S.;Bellini T.
2026-01-01
Abstract
Background: Febrile infants ≤90 days are at high risk of serious bacterial infections, but prompt differentiation between viral and bacterial infections remains a challenge. Host gene expression signatures, particularly those involving the type I interferon (IFN) pathway, show promise as diagnostic tools. This study evaluates the ability of IFN signature to differentiate bacterial from viral infections in this population. Methods: This is a prospective, single-center study. Infants ≤90 days were enrolled. All patients underwent complete blood count, CRP, PCT, and IFN signature, assessed by analyzing the expression of six interferon-stimulated genes. Based on routine investigations, patients were divided into bacterial (BI, n = 8) and non-bacterial infection (non-BI, n = 39) and healthy controls (HC, n = 3). Regression analysis was used to determine the variable’s predictive correlation. Results: Forty-seven febrile infants were enrolled. IFN signature resulted significantly elevated in non-BI compared to BI (p < 0.001) and HC (p = 0.008), even within 12 h of fever onset. IFN demonstrated the highest AUC for predicting BI. Combining IFN with CRP or PCT yielded the most robust predictive models (AUC = 0.99 and 0.98). Conclusions: IFN signature resulted as a promising, reliable predictor of BI versus non-BI in febrile infants. This novel biomarker, combined with others, could improve the management of febrile infants reducing unnecessary antibiotics and hospitalizations. Impact: This is the first study to focus on the IFN signature in febrile infants under 90 days old, adding novel insights into the potential of host immune responses as diagnostic biomarkers. This study demonstrates that the peripheral blood interferon signature, specifically the expression of six IFN-stimulated genes, can distinguish bacterial from non-bacterial infections in febrile infants aged 90 days or younger in the very first hours of fever. The IFN score, when combined with traditional inflammatory markers, offers high sensitivity and specificity, making it a potential diagnostic tool for optimizing treatment and reducing unnecessary interventions.
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