نبذة مختصرة : Background: Invasive pulmonary aspergillosis (IPA) remains a life-threatening opportunistic infection, but can be difficult to diagnose. New biomarkers are therefore needed. Gliotoxin (GT), a secondary metabolite of Aspergillus fumigatus, and bis(methylthio)gliotoxin (bmGT), a degradation product of GT, have been proposed as potential biomarkers. However, these findings have yet to be confirmed.
Objectives: To identify the diagnostic potential of GT and bmGT in serum and bronchoalveolar lavage fluid (BALf) in haematology patients compared to galactomannan (GM).
Materials and Methods: We prospectively collected culture supernatant, serum and BALf from patients with culture-positive IPA and measured GT and bmGT concentrations using ultra high-performance liquid chromatography-quadrupole time of flight mass spectrometry. Galactomannan was detected using a commercially available enzyme immunoassay.
Results: We included 18 patients with proven (n = 6) and probable (n = 12) IPA, all with positive cultures for Aspergillus fumigatus. BmGT was only detected in serum from one patient (5.6%), whereas GM was positive (optical density ≥ 0.5) in 11/18 patients (61.1%, P = 0.002). We could not find GT in any serum sample. In BALf, bmGT was detected in 8/18 patients (44.4%) and GT in 9/18 patients (50%), compared to GM (optical density ≥ 1.0) in all patients (100%).
Conclusions: Gliotoxin and bis(methylthio)gliotoxin had a very poor performance for diagnosing IPA. As other biomarkers are more sensitive and easier to detect, we would not recommend serum or BALf GT/bmGT to be used in the diagnosis of IPA.
(© 2019 Blackwell Verlag GmbH.)
References: Lass-Flörl C, Cuenca-Estrella M. Changes in the epidemiological landscape of invasive mould infections and disease. J Antimicrob Chemother. 2017;72(suppl_1):i5-i11.
Lamoth F, Calandra T. Early diagnosis of invasive mould infections and disease. J Antimicrob Chemother. 2017;72(suppl_1):i19-i28.
Domingo MP, Colmenarejo C, Martínez-Lostao L, et al. Bis(methyl)gliotoxin proves to be a more stable and reliable marker for invasive aspergillosis than gliotoxin and suitable for use in diagnosis. Diagn Microbiol Infect Dis. 2012;73(1):57-64.
Lewis RE, Wiederhold NP, Chi J, et al. Detection of gliotoxin in experimental and human aspergillosis. Infect Immun. 2005;73(1):635-637.
Vidal-García M, Domingo MP, De Rueda B, et al. Clinical validity of bis(methylthio)gliotoxin for the diagnosis of invasive aspergillosis. Appl Microbiol Biotechnol. 2016;100(5):2327-2334.
Svahn S. Analysis of Secondary Metabolites from Aspergillus fumigatus and Penicillium nalgiovense: Antimicrobial Compounds from Filamentous Fungi Isolated from Extreme Environments [Doctoral thesis]. Uppsala, Sweden: Uppsala University;2015.
Sugui JA, Rose SR, Nardone G, et al. Host immune status-specific production of gliotoxin and bis-methyl-gliotoxin during invasive aspergillosis in mice. Sci Rep. 2017;7(1):10977.
Hammarström H, Stjärne Aspelund A, Christensson B, et al. Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high-risk haematology patients. Mycoses. 2018;61(9):623-632.
De Pauw B, Walsh T, Donnelly J, et al. Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813-1821.
Watts KR, Ratnam J, Ang K-H, et al. Assessing the trypanocidal potential of natural and semi-synthetic diketopiperazines from two deep water marine-derived fungi. Bioorg Med Chem. 2010;18(7):2566-2574.
Gao S, Zheng X, Tang Y, Cheng Y, Hu X, Wu J. Development of a fluorescently labeled aptamer structure-switching assay for sensitive and rapid detection of gliotoxin. Anal Chem. 2019;91(2):1610-1618.
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