Interference of confounding factors on the use of (1,3)-beta-D-glucan in the diagnosis of invasive candidiasis in the intensive care unit

Abstract

Invasive fungal infections (IFIs) are an increasing problem in intensive care units (ICUs), and conventional diagnostic methods are not always reliable or timely enough to deliver appropriate antimicrobial therapy. The dosage of fungal antigens in serum is a promising diagnostic technique, but several confounding factors, such as treatment with immunoglobulins (Ig), albumin, or antifungals, could interfere with the correct interpretation of the (1,3)-beta-D-glucan (BG) assay. This study assessed the reliability of the BG assay and the influence of timing and dosage of major confounding factors on circulating levels of IFI biomarkers. 267 ICU patients who underwent a BG assay were retrospectively studied. The timing and dosage of albumin, use of azole treatment, and infusions of intravenous IgG, red blood cells, concentrated platelets, and frozen plasma were analyzed to find possible correlations with the BG results. The sensitivity and specificity of the BG assay were calculated. The BG test in serum showed high sensitivity (82.9 %) but low specificity (56.7 %). The optimal cut-off for the test was 95.9 pg/mL. The mean BG level in proven invasive candidiasis was around 400 pg/mL. The only factor that was found to significantly confound (p < 0.05) the diagnostic performance of the BG assay was the administration of more than 30 g of albumin within 2 days prior to BG testing. The BG assay remains a useful diagnostic test in ICU patients and the levels of BG are useful in evaluating the positive predictive value of this biomarker. The only confounding factor in our study was the use of albumin.

Soluble Intercellular Adhesion Molecule- (sICAM-) 1, Thrombospondin-1, and Vinculin for the Identification of Septic Shock Patients Suffering from an Invasive Fungal Infection

“…This will hopefully be associated with the following most appreciated side effects: (1) primary cost savings (e.g., due to the waiving of expensive antifungal drugs and reduced hospital and ICU stay) and (2) reducing drug resistance rates (with secondary cost savings). Although the combined use of BDG and PCT was recently described to be suitable for early differential diagnosis between candidemia and bacteremia in intensive care units [22], the diagnostic value of BDG for IFI diagnosis is not free of doubts and subject of controversial discussions [37][38][39][40]. In line with that, BDG recently failed to be a suitable biomarker for reliable IFI diagnosis in septic shock within the presented cohort [21].…”

(1,3)-β-D-glucan-based diagnosis of invasive Candida infection versus culture-based diagnosis in patients with sepsis and with an increased risk of invasive Candida infection (CandiSep): study protocol for a randomized controlled trial

“…Elevated BDG serum concentrations of more than 80 pg/ml have a high diagnostic accuracy to predict ICI [12, 13, 18, 33, 34]. However, the available data suggest that many ICU interventions may interfere by increasing BDG serum concentrations [11, 14, 15]. In addition, the diagnostic accuracy of BDG has been reported only for candidemia rather than ICI in general and may also depend on the fungal species [12].…”

“…In addition, falsely increased BDG serum concentrations in the absence of ICI may be induced by several common ICU interventions. For example, concurrent bacteremia, hemodialysis membranes, administrations of blood products, and treatment with albumin or immunoglobulin products can interfere with BDG measurements [11, 14, 15]. If relevant, this type of interference would significantly reduce the clinical usability of BDG assays in critically ill patients.…”

Treatment and management of primary antibody deficiency: German interdisciplinary evidence‐based consensus guideline

“…In IVIg products containing maltose, erroneously elevated blood sugar values can occur when using GDH-PQQ test strips [87]. Diagnostic assays using Beta-D-Glucan for fungal testing can be false positive [88]. Immunoglobulin treatment can transfer antibodies to blood groups, affecting serological test.…”