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. Issue 12 (17th September 2020)

• Record Type: Journal Article
• Authors: Cento, Valeria; Alteri, Claudia; Mancini, Valentina; Gatti, Milo; Lepera, Valentina; Mazza, Ernestina; Moioli, Maria Cristina; Merli, Marco; Colombo, Jacopo; Orcese, Carlo Andrea; Bielli, Alessandra; Torri, Stefania; Gasparini, Laura Elisa; Vismara, Chiara; De Gasperi, Andrea; Brioschi, Paolo; Puoti, Massimo; Cairoli, Roberto; Lombardi, Gianluigi; Perno, Carlo Federico
• Is Part Of: Mycoses. Volume 63:Issue 12(2020)
• Page Start: 1299
• Page End: 1310
• Publication Date: 2020-09-17
• Subjects: antimycotic chemotherapy -- candidaemia -- deep fungal infection -- immunodeficiency -- peritonitis -- surgery -- systemic infection; Pathogenic fungi -- Periodicals; Medical mycology -- Periodicals; 616.969
• DOI: 10.1111/myc.13170
• Languages: English
• ISSNs: 0933-7407

Abstract

Summary: Objectives: Rapid 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. Methods: BDG 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. Results: Patients 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). Conclusions: The 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.