Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-beta-D-glucan, Aspergillus PCR, multifungal DNA-microarray, and Aspergillus azole resistance PCRs in blood and bronchoalveolar lavage samples: results of a prospective multicentre study

Boch, T. and Spiess, B. and Cornely, O. A. and Vehreschild, J. J. and Rath, P. M. and Steinmann, J. and Heinz, W. J. and Hahn, J. and Krause, S. W. and Kiehl, M. G. and Egerer, G. and Liebregts, T. and Koldehoff, M. and Klein, M. and Nolte, F. and Mueller, M. C. and Merker, N. and Will, S. and Mossner, M. and Popp, H. and Hofmann, W-K. and Reinwald, M. and Buchheidt, D. (2016) Diagnosis of invasive fungal infections in haematological patients by combined use of galactomannan, 1,3-beta-D-glucan, Aspergillus PCR, multifungal DNA-microarray, and Aspergillus azole resistance PCRs in blood and bronchoalveolar lavage samples: results of a prospective multicentre study. CLINICAL MICROBIOLOGY AND INFECTION, 22 (10). pp. 862-868. ISSN 1198-743X, 1469-0691

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Abstract

High mortality rates of invasive fungal disease (IFD), especially invasive aspergillosis (IA), in immuno-compromised haematological patients and current diagnostic limitations require improvement of detection of fungal pathogens by defining the optimal use of biomarkers and clinical samples. Concurrent bronchoalveolar lavage (BAL) and peripheral blood samples of 99 haematological patients with suspected IFD were investigated within a multicentre prospective study. Diagnostic performance of a galactomannan (GM) enzyme immune assay (EIA), a 1,3-beta-D-glucan assay (BDG), an Aspergillus PCR, and a multifungal DNA-microarray (Chip) alone or in combination were calculated. IFD were classified as proven (n = 3), probable (n = 34), possible (n = 33), and no IFD (n = 29) according to EORTC/MSG criteria. GM, PCR, and Chip showed superior diagnostic performance in BAL than in blood, whereas specificity of BDG in BAL was poor (48% (14/29)). The combination of GM (BAL) with BDG (blood) showed sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and DOR (diagnostic odds ratio) of 92% (34/37), 93% (27/29), 94%, 90%, and 153.0, respectively. Combining GM (BAL) with PCR (BAL) showed convincing diagnostic potential for diagnosing IA with sensitivity, specificity, PPV, NPV, and DOR of 85% (17/20), 97% (28/29), 94%, 90%, and 158.7. Addition of the DNA-microarray resulted in further detection of two mucormycetes infections. In 1 out of 15 Aspergillus DNA-positive samples a triazole resistance-mediating Cyp51A mutation was found. Combination of biomarkers is superior to their sole use in diagnosing IFD, particularly IA. Integrating blood and BAL samples into a diagnostic algorithm is an advantageous approach. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: LATERAL-FLOW DEVICE; POLYMERASE-CHAIN-REACTION; LINKED-IMMUNOSORBENT-ASSAY; CELL TRANSPLANT RECIPIENTS; PRIMARY CLINICAL-SAMPLES; REAL-TIME PCR; BETA-D-GLUCAN; PULMONARY ASPERGILLOSIS; ENZYME-IMMUNOASSAY; IMMUNOCOMPROMISED PATIENTS; beta-D-glucan; AspergillusPCR; Fungal diagnostics; Galactomannan; Invasive fungal disease; Multifungal DNA-microarray
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 24 Apr 2019 11:51
Last Modified: 24 Apr 2019 11:51
URI: https://pred.uni-regensburg.de/id/eprint/4138

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