Boch, T., Spiess, B., Cornely, O. A., Vehreschild, J. J., Rath, P. M., Steinmann, J., Heinz, W. J., Hahn, J., Krause, S. W., Kiehl, M. G., Egerer, G., Liebregts, T., Koldehoff, M., Klein, M., Nolte, F., Mueller, M. C., Merker, N., Will, S., Mossner, M., Popp, H., Hofmann, W-K., 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. Clin. Microbiol. Infect., 22 (10). S. 862 - 869. OXFORD: ELSEVIER SCI LTD. ISSN 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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Boch, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spiess, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cornely, O. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vehreschild, J. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rath, P. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinmann, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinz, W. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahn, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krause, S. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kiehl, M. G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Egerer, G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liebregts, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koldehoff, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, M. C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merker, N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Will, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mossner, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Popp, H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, W-K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinwald, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buchheidt, D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-261381
DOI: 10.1016/j.cmi.2016.06.021
Journal or Publication Title: Clin. Microbiol. Infect.
Volume: 22
Number: 10
Page Range: S. 862 - 869
Date: 2016
Publisher: ELSEVIER SCI LTD
Place of Publication: OXFORD
ISSN: 1469-0691
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
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 PATIENTSMultiple languages
Infectious Diseases; MicrobiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26138

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