Triacetylfusarinine C: A urine biomarker for diagnosis of invasive aspergillosis. Issue 2 (February 2019)

• Record Type: Journal Article
• Authors: Hoenigl, Martin; Orasch, Thomas; Faserl, Klaus; Prattes, Juergen; Loeffler, Juergen; Springer, Jan; Gsaller, Fabio; Reischies, Frederike; Duettmann, Wiebke; Raggam, Reinhard B.; Lindner, Herbert; Haas, Hubertus
• Is Part Of: Journal of infection. Volume 78:Issue 2(2019)
• Page Start: 150
• Page End: 157
• Publication Date: 2019-02
• Subjects: Aspergillosis -- Biomarker -- Diagnosis -- Siderophore -- Urine; Amb liposomal amphotericin B -- BALF bronchoalveolar lavage fluid -- BGE background electrolyte -- Casp empirical therapy with caspofungin -- CE capillary electrophoresis -- crea creatinine -- EORTC/MSG European Organization for Research and Treatment of Cancer/Mycoses Study Group -- ESI electrospray ionization -- Flu fluconazole -- GM galactomannan -- IA invasive aspergillosis -- ICU submission to intensive care unit -- IQR interquartile range -- LC liquid chromatography -- ms mass spectrometry -- ODI optical density index -- pIA day of diagnosis ``probable invasive aspergillosis" -- Pos posaconazole, TAFC, triacetylfusarinine C -- Tx day of transplantation -- Vor iv voriconazole intravenously; Infection -- Periodicals; Bacterial Infections -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.905
• DOI: 10.1016/j.jinf.2018.09.006
• Languages: English
• ISSNs: 0163-4453

Abstract

Highlights: Diagnosis of invasive aspergillosis (IA) is unsatisfying with current methods. New method for quantification of an Aspergilus siderophore (TAFC) was established. TAFC determination in urine yielded promising results for diagnosing IA. Detection in urine offers the advantage of non-invasive sampling. Summary: 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. Graphical abstract: Image, graphical abstract