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Objectives: Early diagnosis of invasive aspergillosis (IA) remains challenging, with available diagnostics being limited by inadequate sensitivities and specificities. Triacetylfusarinine C, a fungal siderophore that has been shown to accumulate in urine in animal models, is a potential new biomarker for diagnosis of IA., Methods: We developed a method allowing absolute and matrix-independent mass spectrometric quantification of TAFC. Urine TAFC, normalized to creatinine, was determined in 44 samples from 24 patients with underlying hematologic malignancies and probable, possible or no IA according to current EORTC/MSG criteria and compared to other established biomarkers measured in urine and same-day blood samples., Results: TAFC/creatinine sensitivity, specificity, positive and negative likelihood ratio for probable versus no IA (cut-off ≥ 3) were 0.86, 0.88, 6.86, 0.16 per patient., Conclusion: For the first time, we provide proof for the occurrence of TAFC in human urine. TAFC/creatinine index determination in urine showed promising results for diagnosis of IA offering the advantages of non-invasive sampling. Sensitivity and specificity were similar as reported for GM determination in serum and bronchoalveolar lavage, the gold standard mycological criterion for IA diagnosis., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Aspergillus spp. induce elevated levels of several cytokines. It remains unknown whether these cytokines hold value for clinical routine and enhance diagnostic performances of established and novel biomarkers/tests for invasive aspergillosis (IA)., Methods: This cohort study included 106 prospectively enrolled (2014-2017) adult cases with underlying hematological malignancies and suspected pulmonary infection undergoing bronchoscopy. Serum samples were collected within 24 hours of bronchoalveolar lavage fluid (BALF) sampling. Both, serum and BALF samples were used to evaluate diagnostic performances of the Aspergillus-specific lateral-flow device test (LFD), Aspergillus PCR, β-D-glucan, and cytokines that have shown significant associations with IA before., Results: Among 106 cases, 11 had probable IA, and 32 possible IA; 80% received mold-active antifungals at the time of sampling. Diagnostic tests and biomarkers showed better performance in BALF versus blood, with the exception of serum interleukin (IL)-8 which was the most reliable blood biomarker. Combinations of serum IL-8 with either BALF LFD (sensitivity 100%, specificity 94%) or BALF PCR (sensitivity 91%, specificity 97%) showed promise for differentiating probable IA from no IA., Conclusions: High serum IL-8 levels were highly specific, and when combined with either the BALF Aspergillus-specific LFD, or BALF Aspergillus PCR also highly sensitive for diagnosis of IA., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The aim of this combined in-vitro and in-vivo study was to investigate whether state of the art dialysis modalities produce false positive serum 1,3-ß-d-Glucan (BDG) levels., Methods: Dialysis fluid for simulated dialysis treatments was spiked with BDG from different sources. Samples were taken from the dialysate and dialyzer blood compartments at various time points. In addition, serum samples were obtained in three groups of patients without invasive fungal disease: a.) twelve patients on chronic hemodialysis (HD)/hemodiafiltration (HDF); b.) ten patients on continuous ambulatory peritoneal dialysis (CAPD); and c.) ten patients with stable chronic kidney disease (CKD) but without dialysis., Results: Median BDG levels in BDG spiked dialysate were 3250.9, 2050.4, and 390.1 pg/ml respectively. All corresponding samples from the blood compartments were BDG negative. In HD/HDF patients no increase of serum BDG levels could be observed over the duration of treatment. 71/72 BDG tests in this group remained negative. BDG tests were also negative in 9/10 CAPD patients, both in in- and outflow dialysates as well as in all ten patients with CKD., Conclusion: We conclude that state of the art renal replacement therapies using up-to-date treatments are not a cause of falsely elevated serum BDG levels., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to investigate the prognostic potential of 1,3-beta-d-glucan (BDG) testing in bronchoalveolar lavage fluid (BALF) samples., Methods: A total of 300 BALF samples from 252 patients were investigated for BDG (Fungitell(®) assay). Prognostic potential of BALF BDG was evaluated by using: i.) Kaplan-Meier analysis, and ii.) multivariable Cox hazard regression analyses., Results: BALF BDG levels were found to be significantly higher in samples with Candida spp. colonization (p < 0.001). A total of 61/252 patients (24.2%) died within 90-days of BALF sampling (18.1% of patients with BALF BDG <200 pg/mL, 32.4% with BALF BDG ≥200 pg/mL). Kaplan-Meier analysis revealed that overall cumulative 90-day mortality was significantly higher in those with BALF BDG levels ≥200 pg/mL when compared to those with levels <200 pg/mL (log-rank p = 0.006, Breslow p = 0.005 and Tarone-Ware p = 0.005). The multivariable Cox regression analysis showed that BALF BDG levels were a strong predictor of 90-day overall mortality, with a hazard ratio of 1.048 (per 100 pg/mL increase of BALF BDG)., Conclusion: False positive BALF BDG results in the presence of Candida spp. colonization of the lower respiratory tract may explain the limited diagnostic potential of BALF BDG testing. In contrast, prognostic potential of BALF BDG may be promising., (Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)