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

Magdalena Mnichowska-Polanowska^1*Bartłomiej Grygorcewicz^2,3Barbara Dolegowska⁴Agnieszka Boroń⁵Agata Michnowska^6,7Konrad Jarosz⁸Magdalena Adamowicz⁹Bartosz Wojciuk⁷

• ¹Pomeranian Medical University in Szczecin, Department of Microbiology, immunology and Laboratory Medicine, Szczecin, Poland
• ²Pomeranian Medical University in Szczecin, Department of Genomics and Forensic Genetics, Szczecin, Poland
• ³Pomeranian Medical University in Szczecin, Regional Center for Digital Medicine, Szczecin, Poland
• ⁴Pomeranian Medical University in Szczecin, Department of Laboratory Medicine, Szczecin, Poland
• ⁵Pomeranian Medical University in Szczecin, Department of Clinical and Molecular Biochemistry, Szczecin, Poland
• ⁶Teaching Hospital no 2 of Pomeranian Medical University in Szczecin, Clinic of Nephrology, Internal Medicine and Transplantation., Szczecin, Poland
• ⁷Pomeranian Medical University in Szczecin, Department of Immunological Diagnostics, Szczecin, Poland
• ⁸Teaching Hospital no 1 of Pomeranian Medical University in Szczecin, Clinic of Anaesthesiology and Intensive Therapy, Szczecin, Poland
• ⁹Teaching Hospital no 2 of Pomeranian Medical University in Szczecin, Clinic of Anaesthesiology and Intensive Therapy, Szczecin, Poland

Objectives: 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. 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]. Conclusions 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.