Combined Use of Presepsin and (1,3)-β-D-glucan as Biomarkers for Diagnosing Candida Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients

Abstract: New biomarker panel was developed and validated on 165 critically ill adult patients to enable a more accurate invasive candidiasis (IC) diagnosis. Serum levels of the panfungal biomarker (1,3)-β-D-glucan (BDG) and the inflammatory biomarkers C-reactive protein, presepsin (PSEP), and procalcitonin (PCT) were correlated with culture-confirmed candidemia or bacteremia in 58 and 107 patients, respectively. The diagnostic utility was evaluated in sensitivity, specificity, positive pre- dictive value (PPV), and negative predictive value (NPV). BDG was the best marker for IC, achieving 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 but had a lower PPV (36.5%) and low specificity (5.6%). Combined use of PSEP and BDG, thus, seems to be the most powerful laboratory approach for diagnosing IC. Furthermore, PSEP was more accurate for 28-day mortality prediction the area under the receiver operating characteristic curve (AUC = 0.74) than PCT (AUC = 0.31; PCT cut-off = 0.5 ng/mL). Finally, serum PSEP levels decreased significantly after only 14 days of echinocandin therapy (p = 0.0012). The probability of IC is almost 100% in critically ill adults with serum BDG and PSEP concentrations > 200 pg/mL and >700 pg/mL, respectively, defining a borderline between non-invasive superficial Candida colonization and IC.

Keywords: sepsis; Candida; bloodstream infections; presepsin; procalcitonin; C-reactive protein; (1,3)-β-D-glucan