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

## TL;DR

This study identifies a three-protein inflammatory signature that can distinguish isolated fungal infections from combined fungal and bacterial infections in critically ill patients.

## Contribution

The study introduces a novel three-protein inflammatory signature for differentiating isolated candidemia from candidemia with bacterial co-infection.

## Key findings

- LAP-TGF beta-1 effectively distinguishes isolated candidemia with high accuracy (AUC 0.95).
- TRANCE and IL-17C show potential as indicators of bacterial co-infection in candidemia.
- A three-protein panel achieves moderate to high discrimination (AUC 0.82) between isolated and co-infection cases.

## Abstract

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

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.

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.

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.

Flowchart illustrating the diagnostic efficiency of inflammatory signatures to distinguish isolated candidemia from candidemia with bacterial co-infection. It outlines study design, eligibility criteria, and outcomes. Critically ill patients are analyzed for three protein inflammatory signatures: LAP-TGF beta-1, TRANCE, and IL-17C. These effectively discriminate between isolated candidemia and candidemia with bacterial co-infection. The process involves protein expression analysis, multiple-group comparison, pairwise comparison, and five-fold cross-validation, with a final focus on the inflammatory signature and its implications.