Invasive fungal disease (IFD) early diagnosis improves hematological patient survival. Non-culture-based methods may reduce diagnostic time to identify IFD. As complex data on the value of 1,3-β-D-glucan (BDG) from bronchoalveolar lavage fluid (BALF) compared to serum for the most frequent invasive pulmonary aspergillosis (IPA) diagnosis are scarce, particularly including evaluation of potential factors adversely affecting BDG assay, we provided prospective single-center analysis evaluating 172 episodes of pulmonary infiltrates with BDG detection in BALF and serum samples collected in parallel among hematological patients from 2006 to 2015. Proven and probable IPA were documented in 13.4% of the episodes. Sensitivity (SEN), specificity (SPE), positive and negative predictive value (PPV; NPV), and diagnostic odds ratio (DOR) of the BDG assay using standard (80 pg/ml) cut-off for BALF were: 56.5%; 83.2%; 34.2%; 92.5%, and 6.5, respectively, and for serum were: 56.5%; 82.6%; 33.3%; 92.5%, and 6.2, respectively. The same BDG assay parameters employing a calculated optimal cut-off for BALF (39 pg/ml) were: 78.3%; 72.5%; 30.5%; 95.6%, and 9.5, respectively; and for serum (40 pg/ml) were: 73.9%; 69.1%; 27.0%; 94.5%, and 6.3, respectively. While identifying acceptable SEN, SPE, and DOR, yet low PPV of both BALF and serum BDG assay for IPA diagnosis, neither the combination of both materials nor the new optimal BDG cut-off led to significant test quality improvement. Absolute neutrophil count and aspirated BALF volume with a significant trend affected BDG assay performance. The BDG test did not outperform galactomannan assay.

CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Clinical Microbiology University Hospital Brno Czech Republic

Department of Internal Medicine Hematology and Oncology Masaryk University and University Hospital Brno Czech Republic

Department of Mathematics and Statistics Faculty of Science Masaryk University Brno Czech Republic

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Herbrecht R, Bories P, Moulin J-C, Ledoux M-P, Letscher-Bru V. Risk stratification for invasive aspergillosis in immunocompromised patients. Ann. N. Y. Acad. Sci. 2012;1272:23–30. doi: 10.1111/j.1749-6632.2012.06829.x. PubMed DOI

Pagano L, et al. Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients. J. Antimicrob. Chemother. 2011;66(Suppl 1):i5–14. doi: 10.1093/jac/dkq437. PubMed DOI

Racil Z, et al. Invasive aspergillosis in patients with hematological malignancies in the Czech and Slovak republics: fungal infection database (FIND) analysis, 2005–2009. Int. J. Infect. Dis. 2013;17:e101–109. doi: 10.1016/j.ijid.2012.09.004. PubMed DOI

De Pauw B, 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;46:1813–1821. doi: 10.1086/588660. PubMed DOI PMC

Donnelly JP, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin. Infect. Dis. 2019 doi: 10.1093/cid/ciz1008. PubMed DOI PMC

Neofytos D, et al. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of Multicenter Prospective Antifungal Therapy (PATH) Alliance registry. Clin. Infect. Dis. 2009;48:265–273. doi: 10.1086/595846. PubMed DOI

Freifeld AG, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2011;52:427–431. doi: 10.1093/cid/ciq147. PubMed DOI

White SK, Walker BS, Hanson KE, Schmidt RL. Diagnostic accuracy of β-d-glucan (fungitell) testing among patients with hematologic malignancies or solid organ tumors: a systematic review and meta-analysis. Am. J. Clin. Pathol. 2019;151:275–285. doi: 10.1093/ajcp/aqy135. PubMed DOI

Patterson TF, et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2016;63:e1–e60. doi: 10.1093/cid/ciw326. PubMed DOI PMC

Pappas PG, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin. Infect. Dis. 2016;62:e1–50. doi: 10.1093/cid/civ1194. PubMed DOI PMC

D’Haese J, et al. Detection of galactomannan in bronchoalveolar lavage fluid samples of patients at risk for invasive pulmonary aspergillosis: analytical and clinical validity. J. Clin. Microbiol. 2012;50:1258–1263. doi: 10.1128/JCM.06423-11. PubMed DOI PMC

Leeflang MMG, et al. Galactomannan detection for invasive aspergillosis in immunocompromised patients. Cochrane Database Syst. Rev. 2015 doi: 10.1002/14651858.CD007394.pub2. PubMed DOI PMC

Mennink-Kersten MASH, Donnelly JP, Verweij PE. Detection of circulating galactomannan for the diagnosis and management of invasive aspergillosis. Lancet Infect. Dis. 2004;4:349–357. doi: 10.1016/S1473-3099(04)01045-X. PubMed DOI

Hou T-Y, et al. The screening performance of serum 1,3-β-d-glucan in patients with invasive fungal diseases: a meta-analysis of prospective cohort studies. PLoS ONE. 2015;10:e0131602. doi: 10.1371/journal.pone.0131602. PubMed DOI PMC

Lamoth F, et al. β-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of cohort studies from the third European conference on infections in leukemia (ECIL-3) Clin. Infect. Dis. 2012;54:633–643. doi: 10.1093/cid/cir897. PubMed DOI

He S, et al. A systematic review and meta-analysis of diagnostic accuracy of serum 1,3-β-d-glucan for invasive fungal infection: focus on cutoff levels. J. Microbiol. Immunol. Infect. 2015;48:351–361. doi: 10.1016/j.jmii.2014.06.009. PubMed DOI

Azoulay E, et al. (1, 3)-β-d-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies. Oncotarget. 2016;7:21484–21495. doi: 10.18632/oncotarget.7471. PubMed DOI PMC

Levesque E, et al. Detection of (1,3)-β-d-glucan for the diagnosis of invasive fungal infection in liver transplant recipients. Int. J. Mol. Sci. 2017;18:862. doi: 10.3390/ijms18040862. PubMed DOI PMC

Prattes J, et al. Novel tests for diagnosis of invasive aspergillosis in patients with underlying respiratory diseases. Am. J. Respir. Crit. Care Med. 2014;190:922–929. doi: 10.1164/rccm.201407-1275OC. PubMed DOI

Ostrosky-Zeichner L, et al. Multicenter clinical evaluation of the (1 → 3) beta-d-glucan assay as an aid to diagnosis of fungal infections in humans. Clin. Infect. Dis. 2005;41:654–659. doi: 10.1086/432470. PubMed DOI

Acosta J, et al. A prospective comparison of galactomannan in bronchoalveolar lavage fluid for the diagnosis of pulmonary invasive aspergillosis in medical patients under intensive care: comparison with the diagnostic performance of galactomannan and of (1 → 3)-β-d-glucan chromogenic assay in serum samples. Clin. Microbiol. Infect. 2011;17:1053–1060. doi: 10.1111/j.1469-0691.2010.03357.x. PubMed DOI

Shi X-Y, et al. Diagnostic value of (1 → 3)-β-d-glucan in bronchoalveolar lavage fluid for invasive fungal disease: a meta-analysis. Respir. Med. 2016;117:48–53. doi: 10.1016/j.rmed.2016.05.017. PubMed DOI

Rose SR, et al. The utility of bronchoalveolar lavage beta-d-glucan testing for the diagnosis of invasive fungal infections. J. Infect. 2014;69:278–283. doi: 10.1016/j.jinf.2014.04.008. PubMed DOI PMC

Mutschlechner W, et al. Bronchoalveolar lavage fluid (1,3)β-d-glucan for the diagnosis of invasive fungal infections in solid organ transplantation: a prospective multicenter study. Transplantation. 2015;99:e140–144. doi: 10.1097/TP.0000000000000635. PubMed DOI

Theel ES, et al. Detection of (1, 3)-β-d-glucan in bronchoalveolar lavage and serum samples collected from immunocompromised hosts. Mycopathologia. 2013;175:33–41. doi: 10.1007/s11046-012-9579-y. PubMed DOI

Boch T, et al. Detection of invasive pulmonary aspergillosis in critically ill patients by combined use of conventional culture, galactomannan, 1-3-beta-d-glucan and Aspergillus specific nested polymerase chain reaction in a prospective pilot study. J. Crit. Care. 2018;47:198–203. doi: 10.1016/j.jcrc.2018.07.001. PubMed DOI

Weinbergerova B, Kocmanova I, Racil Z, Mayer J. Serological approaches. Methods Mol. Biol. 2017;1508:209–221. doi: 10.1007/978-1-4939-6515-1_11. PubMed DOI

Pickering JW, Sant HW, Bowles CAP, Roberts WL, Woods GL. Evaluation of a (1 → 3)-beta-d-glucan assay for diagnosis of invasive fungal infections. J. Clin. Microbiol. 2005;43:5957–5962. doi: 10.1128/JCM.43.12.5957-5962.2005. PubMed DOI PMC

Mennink-Kersten MASH, Ruegebrink D, Verweij PE. Pseudomonas aeruginosa as a cause of 1,3-beta-d-glucan assay reactivity. Clin. Infect. Dis. 2008;46:1930–1931. doi: 10.1086/588563. PubMed DOI

Albert O, et al. Reactivity of (1 → 3)-β-d-glucan assay in bacterial bloodstream infections. Eur. J. Clin. Microbiol. Infect. Dis. 2011;30:1453–1460. doi: 10.1007/s10096-011-1244-8. PubMed DOI

Ellis M, et al. Assessment of the clinical utility of serial beta-d-glucan concentrations in patients with persistent neutropenic fever. J. Med. Microbiol. 2008;57:287–295. doi: 10.1099/jmm.0.47479-0. PubMed DOI

Racil Z, et al. Difficulties in using 1,3-{beta}-d-glucan as the screening test for the early diagnosis of invasive fungal infections in patients with haematological malignancies-high frequency of false-positive results and their analysis. J. Med. Microbiol. 2010;59:1016–1022. doi: 10.1099/jmm.0.019299-0. PubMed DOI

Racil Z, et al. Galactomannan detection in bronchoalveolar lavage fluid for the diagnosis of invasive aspergillosis in patients with hematological diseases-the role of factors affecting assay performance. Int. J. Infect. Dis. 2011;15:e874–881. doi: 10.1016/j.ijid.2011.09.011. PubMed DOI

Hoenigl M, et al. Performance of galactomannan, beta-d-glucan, Aspergillus lateral-flow device, conventional culture, and PCR tests with bronchoalveolar lavage fluid for diagnosis of invasive pulmonary aspergillosis. J. Clin. Microbiol. 2014;52:2039–2045. doi: 10.1128/JCM.00467-14. PubMed DOI PMC

Current and Future Pathways in Aspergillus Diagnosis