Presepsin and (1,3)-β-D-Glucan as a Tool for Predicting Candida Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients

Background: To improve the accuracy in invasive candidiasis diagnostics, a new biomarker panel has been developed and validated on a 165-patient cohort of critically ill adults.Methods: The serum levels of inflammatory biomarkers, C-reactive protein, presepsin (PSEP), procalcitonin (PCT), and of panfungal (1,3)-β-D-glucan (BDG), were correlated with culture-confirmed candidemia or bacteremia in 58 or 107 patients, respectively. The diagnostic effect of the host and pathogen biomarkers was expressed using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).Results: For invasive candidiasis, the best performing BDG exhibited 96.6% sensitivity, 97.2% specificity, 94.9% PPV and 98.1% NPV at a cut-off of 200 pg/mL (P ≤ 0.001). PSEP exhibited 100% sensitivity and 100% NPV at a cut-off of 700 pg/mL. Furthermore, PSEP was more accurate for 28-day mortality prediction (AUC = 0.74) than PCT (AUC = 0.31; PCT cut-off 0.5 ng/mL). Finally, PSEP showed a significant serum decrease as early as 14 days after echinocandin therapy initiation (P = 0.0012).Conclusions: At concentrations of BDG > 200 pg/mL and PSEP > 700 pg/mL, the probability of invasive candidiasis in critically ill adults is close to 100% defining a borderline between non-invasive superficial Candida colonization and invasive candidiasis.Trial registration: The study was approved by the University Hospital Ostrava Ethics Committee for Multicenter Clinical Trials (no. 448/2018) and registered in ClinicalTrials.gov (ID: NCT03584594), date of registration June 28,2018.