Quantification of 1,3‐β‐d‐glucan by Wako β‐glucan assay for rapid exclusion of invasive fungal infections in critical patients: A diagnostic test accuracy study

• DOI: 10.1111/myc.13170
• Publication Date: 2020-08-28T06:22:37Z
• Authors: Valeria Cento; Claudia Alteri; Valentina Mancini; Milo Gatti; Valentina Lepera; Ernestina Mazza; Maria Cristina Mo...; Marco Merli; Jacopo Colombo; Carlo Andrea Orcese; Alessandra Bielli; Stefania Torri; Laura Elisa Gaspa...; Chiara Vismara; Andrea De Gasperi; Paolo Brioschi; Massimo Puoti; Roberto Cairoli; Gianluigi Lombardi; Carlo Federico Perno
• Keywords: Male; 0301 basic medicine; Antifungal Agents; beta-Glucans; Diagnostic Tests, Routine; Middle Aged; Sensitivity and Specificity; 3. Good health; Intensive Care Units; 03 medical and health sciences; Caspofungin; Limit of Detection; Predictive Value of Tests; Humans; antimycotic chemotherapy; candidaemia; deep fungal infection; immunodeficiency; peritonitis; surgery; systemic infection; Aged; Antifungal Agents; Caspofungin; Diagnostic Tests, Routine; Female; Fluconazole; Humans; Intensive Care Units; Invasive Fungal Infections; Limit of Detection; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Voriconazole; beta-Glucans; antimycotic chemotherapy; candidaemia; deep fungal infection; immunodeficiency; peritonitis; surgery; systemic infection;; Female; Voriconazole; antimycotic chemotherapy; candidaemia; deep fungal infection; immunodeficiency; peritonitis; surgery; systemic infection; Fluconazole; Invasive Fungal Infections; Aged; Retrospective Studies

SummaryObjectivesRapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available β‐d‐Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut‐off values for IFI exclusion.MethodsBDG results by Wako β‐glucan assay (lower limit of detection [LLOD] = 2.16 pg/mL, positivity ≥ 11 pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N = 42), intensive care units (ICUs; N = 80), or other wards (N = 48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values.ResultsPatients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values < LLOD performed within a median of 1 (interquartile range: 1‐3) day were able to exclude a proven IFI with 100% sensitivity and negative predictive value (primary study goal). Test's specificity improved by using two distinct positivity and negativity cut‐offs (7.7 pg/mL and LLOD, respectively), but remained suboptimal in ICU patients (50%), as compared to haematological or other patients (93% and 90%, respectively).ConclusionsThe classification of Wako's results as negative when < LLOD, and positive when > 7.7 pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non‐ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.