Use and Limits of (1-3)-β- d -Glucan Assay (Fungitell), Compared to Galactomannan Determination (Platelia Aspergillus), for Diagnosis of Invasive Aspergillosis

Abstract

f This study was undertaken to examine the performance of the Fungitell ␤-glucan (BG) assay, to compare it with that of the galactomannan (GM) test for the diagnosis of invasive aspergillosis (IA) in patients with hematological malignancies, and to examine the rates of false-positive BG and GM test results due to ␤-lactam antibiotics among sera of patients with Gram-positive or Gram-negative bacteremia and selected sera with false-positive results from the GM test. Serum samples from 105 patients with proven (n ‫؍‬ 14) or probable (n ‫؍‬ 91) IA, 97 hematology patients at risk for invasive fungal infections, 50 healthy blood donors, and 60 patients with bacteremia were used to study the sensitivities and specificities of the assays. The GM test was more specific than the BG assay (97% versus 82%, respectively; P ‫؍‬ 0.0001) and the BG assay was more sensitive than the GM test (81% versus 49%, respectively; P < 0.0001) for IA diagnosis. The study of 49 separate batches of ␤-lactam antibiotics showed high and very similar rates of false-positive results for the GM and BG assays (29 and 33%, respectively; P ‫؍‬ 0.82) but with an almost complete lack of concordance between the 2 assays. For patients with bacteremia, the rate of false-positive results was much higher with the BG test than with the GM test (37% versus 2%, respectively; P < 0.0001), with no significant difference between Gram-positive and Gram-negative bacteremia. In conclusion, the BG test may be useful for the diagnosis of IA because of its high sensitivity in comparison with the GM test, but the overall benefit of this assay remains limited because of its inadequate specificity and its cost.

Usefulness of Two Aspergillus PCR Assays and Aspergillus Galactomannan and β- d -Glucan Testing of Bronchoalveolar Lavage Fluid for Diagnosis of Chronic Pulmonary Aspergillosis

“…in BALF (15), the intake of soy protein (16), intestinal colonization by Bifidobacterium bifidum (17), and Cryptococcus neoformans infection (18) may lead to false-positive results from GM tests. The use of cellulose membranes during hemodialysis, thrombocyte infusion with leukocyteremoving filters, the administration of human blood products (immunoglobulins or albumins), the use of antibiotics such as amoxicillin-clavulanate or piperacillin-tazobactam, severe bacterial infections, and the use of surgical gauzes containing glucan may lead to false-positive results from ␤DG tests (19). Additionally, environmental fungal contamination and commensal organisms such as Candida spp.…”

β- d -Glucan Screening for Detection of Invasive Fungal Disease in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

“…There are a number of factors reported that may lead to false-positive results of the BDG assay, such as severe mucositis (19), the administration of albumin and immunoglobulins (20), thrombocyte infusion with leukocyte-removing filters, or the administration of antibiotics, such as amoxicillin-clavulanate or piperacillin-tazobactam (6). Although some authors argue that bacteremia is an improbable cause of a positive BDG assay (21), one recent study found a significant higher rate of false-positive BDG tests in bacteremic patients, independently of Gram-positive or Gram-negative bacteremia (6).…”

“…There are a number of factors reported that may lead to false-positive results of the BDG assay, such as severe mucositis (19), the administration of albumin and immunoglobulins (20), thrombocyte infusion with leukocyte-removing filters, or the administration of antibiotics, such as amoxicillin-clavulanate or piperacillin-tazobactam (6). Although some authors argue that bacteremia is an improbable cause of a positive BDG assay (21), one recent study found a significant higher rate of false-positive BDG tests in bacteremic patients, independently of Gram-positive or Gram-negative bacteremia (6). Importantly, transient candidemia has been reported as a cause of persistent false-positive BDG levels (22), a True-positive (TP) and false-negative (FN) results refer to all BDG values assessed at the time of the potential onset of IFD (e.g., four, two, and zero weeks prior to the first pathological sign, such as blood culture results or biopsy, pathological imaging, or galactomannan positivity); all subsequent levels of BDG were considered a response control for therapy and were not included in the analysis.…”

“…Whereas the cell wall polysaccharide component GM is released by all Aspergillus species and can be detected in patients with invasive aspergillosis (IA), BDG can be detected in patients with IFD due to Aspergillus and Candida spp., Fusarium, Trichosporon, or Saccharomyces, and Pneumocystis jirovecii but also in various bacterial infections and even in healthy individuals (5). A number of factors, such as the concomitant administration of various antibiotic compounds, may result in false positivity, whereas systemic mold-active prophylaxis may increase the number of false-negative results (6,7).…”

Molecular Diagnostic Testing for Aspergillus

“…Fungal culture, however, is relatively slow and insensitive, while histopathology and radiographic imaging are not organism specific. The use of fungal cell wall biomarkers, such as 1,3-␤-D-glucan or Aspergillus galactomannan antigen, has improved early diagnosis of IA, but these methods also have significant limitations, including poor sensitivity in certain patient groups (3) and issues with nonspecificity (4). There has been significant recent interest in the use of molecular diagnostics to aid in the rapid and accurate diagnosis of aspergillosis.…”