Martin Hoenigl1, Thomas Orasch2, Klaus Faserl3, Juergen Prattes4, Juergen Loeffler5, Jan Springer5, Fabio Gsaller2, Frederike Reischies6, Wiebke Duettmann6, Reinhard B Raggam7, Herbert Lindner8, Hubertus Haas9. 1. Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria; CBmed Center for Biomarker Research in Medicine, Graz, Austria; Division of Infectious Diseases, Department of Medicine, University of California San Diego, San Diego, CA, USA. 2. Division of Molecular Biology, Medical University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. 3. Division of Clinical Biochemistry, Medical University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. 4. Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria; CBmed Center for Biomarker Research in Medicine, Graz, Austria. 5. Department for Internal Medicine II, University of Wuerzburg Medical Centre, Wuerzburg, Germany. 6. Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria. 7. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Division of Angiology, Medical University of Graz, Graz, Austria. 8. Division of Clinical Biochemistry, Medical University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: herbert.lindner@i-med.ac.at. 9. Division of Molecular Biology, Medical University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: hubertus.haas@i-med.ac.at.
Abstract
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.
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.
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