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

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.

The Comparative Evaluation of the Fujifilm Wako β-Glucan Assay and Fungitell Assay for Diagnosing Invasive Fungal Disease

“…A 5 pg/mL cutoff was optimum for the diagnosis of IFD using the Fujifilm Wako assay with a sensitivity of 79.4% and specificity of 88.3%. Previously, a study by Cento et al revealed that the single quantification of serum BDG using the Fujifilm Wako assay had a sensitivity of 56%, specificity of 87%, NPV of 85%, and PPV of 59% at the cutoff of 11 pg/mL in critically ill ICU and non-ICU patients [ 10 ]. Lowering the cutoff to 7.7 pg/mL, the sensitivity, specificity, NPV, and PPV were 56%, 87%, 85%, and 59%, respectively, similar to our findings [ 10 ].…”

“…Previously, a study by Cento et al revealed that the single quantification of serum BDG using the Fujifilm Wako assay had a sensitivity of 56%, specificity of 87%, NPV of 85%, and PPV of 59% at the cutoff of 11 pg/mL in critically ill ICU and non-ICU patients [ 10 ]. Lowering the cutoff to 7.7 pg/mL, the sensitivity, specificity, NPV, and PPV were 56%, 87%, 85%, and 59%, respectively, similar to our findings [ 10 ]. Lower cutoffs for the Fujifilm Wako assay have been proposed previously.…”

Management of bacterial and fungal infections in cirrhosis: The MDRO challenge

“…More importantly, this biomarker has good negative predictive value when combined with clinical risk stratification and can therefore be used to rule out IFIs in clinical practice. 102 Another cell-wall marker of IFI is galactomannan (GM). GM is produced by Aspergillus spp, Penicillium spp and Histoplasma spp.…”

Diagnosis and Management of Invasive Candida Infections in Critically Ill Patients

“…and Pneumocystis jirovecii as well. Two assays are commercially available, 61,62 with no fixed cutoff values. 63 Across different studies, BDG has been shown to have a relatively high sensitivity (80%) and low specificity (55-60%).…”