What should be the optimal cut-off of serum 1,3-ß-D-glucan for the detection of invasive pulmonary aspergillosis in patients with haematological malignancies?

BACKGROUND: The detection of 1,3-ß-d-glucan (BDG), a cell wall component of several medically important fungi, is a promising tool for the diagnosis of invasive pulmonary aspergillosis. The aim of this study was to evaluate the diagnostic accuracy of the BDG test in invasive pulmonary aspergillosis (IPA) by focusing on the optimal cut-off value. METHODS: The records of the Infection Control Committee were reviewed to identify patients with haematological malignancies and stem cell transplantation who had at least 1 BDG (Fungitell kit) measurement during the period January 2008 through April 2011. The European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria (independent of BDG results) were used to categorize the patients with IPA. Patients with possible IPA were not included in the study. RESULTS: A total of 128 patients (50 with proven or probable IPA) were included in the study. At the manufacturer's recommended cut-off value of 80 pg/ml, the sensitivity of BDG was 66% (95% CI 51.2-78.7), specificity 75.6% (95% CI 64.6-84.5), positive predictive value (PPV) 63.4%, and negative predictive value (NPV) 77.6%. A receiver operating characteristic (ROC) curve was constructed to define the optimum serum BDG cut-off for the diagnosis of IPA. At a cut-off value of 181 pg/ml, the sensitivity was 52% (95% CI 37.4-66.3), specificity 94.8% (95% CI 87.4-98.6), PPV 86.7%, and NPV 75.5%. CONCLUSIONS: Although higher cut-off levels increased the specificity of the BDG test, sensitivity decreased to an unacceptable level; the commercially recommended cut-off value appears to be appropriate for screening purposes.

A methodology for the selection of a routine purity test for insoluble beta(1-->3)glucan.

Beta(1-->3)glucan isolated from the cell wall of Saccharomyces cerevisiae is a biological response modifier (BRM) stimulating resistance against bacterial, viral, fungal and protozoal diseases. This polysaccharide has a high molecular weight, which makes it very difficult to achieve a purity test. A comparative study of different analytical procedures for beta(1-->3)glucan from S. cerevisiae was conducted in order to establish a reliable routine analytical methodology for quality control of this active ingredient in pharmaceutical products. With this aim, different combinations of the analytical procedure steps were tested, including three alternatives for the acid hydrolysis step, three for neutralization, two for gas-liquid chromatographic derivatization and two internal standards. The glucose yield, precision, time consumption and reagent cost per sample were determined for 10 sample replicates. All gas chromatographic determinations were conducted using packed GLC columns and an FID detector. The selected analytical method showed 83.61 +/- 3.48% glucose yield, the shortest relative time consumption (54.2%) and the lowest cost of reagents (7.4%) and consisted of a combination of 72% sulfuric acid hydrolysis, 25% ammonium hydroxide neutralization and alditol acetate derivatization using xylose as internal standard.