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Diagnostic efficiency of inflammatory signatures to distinguish isolated candidemia from candidemia with bacterial co-infection

Frontiers in Immunology, 2025

Mnichowska-Polanowska M., Grygorcewicz B., Dołęgowska B., Boroń A., Michnowska A., Jarosz K., Adamowicz M., Wojciuk B.

Disease areaApplication areaSample typeProducts
Infectious Diseases
Patient Stratificaton
Serum
Olink Target 96

Olink Target 96

Abstract

Introduction

To identify the differences in inflammatory response between critically ill patients responding to combined bacterial-fungal sepsis and those with isolated fungal sepsis.

Methods

A retrospective case-control study compared ICU patients who were exposed (n=24) and unexposed (n=20) to candidemia. Two exposure modes were analyzed: isolated candidemia (C; n=12) versus candidemia with bacterial co-infection (BC; n=12). Targeted proximity extension assay (PEA) was used to examine differences in serum inflammatory proteome between groups. Differential inflammatory proteins served as input for a logistic regression model to validate their effectiveness in discrimination.

Results

Two major clusters—candidemia cases and controls—were identified based on differential protein expression analysis. In five-fold cross-validation, LAP-TGF beta-1 was identified as the main driver, effectively distinguishing isolated candidemia [AUC 0.95; 95% CI 0.853–1.000]. TRANCE and IL-17C showed potential as a diagnostic signature indicating bacterial co-infection in the context of candidemia.

Discussion

The three-protein logistic regression panel (LAP-TGF beta-1, TRANCE and IL-17C) differentiated cases with isolated candidemia from those with candidemia and bacterial co-infection [AUC 0.82; 95% CI 0.629–0.968]. A three-protein inflammatory signature distinguished isolated fungal sepsis from combined bacterial-fungal sepsis. This study is the first to explore the inflammatory response to differentiate isolated candidemia from candidemia with bacterial co-infection.

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