Maximizing Yield and Speed of Fungal Pathogen Identification with Molecular Testing Performed Directly on Patient Specimens

Author:

Lieberman Joshua A.ORCID,Bourassa Lori A.ORCID

Publisher

Springer Science and Business Media LLC

Subject

Infectious Diseases

Reference92 articles.

1. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, 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):1813–21.

2. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, 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. 2020;71(6):1367–76.

3. • Lieberman JA, Bryan A, Mays JA, Stephens K, Kurosawa K, Mathias PC, et al. High Clinical Impact of Broad-Range Fungal PCR in Suspected Fungal Sinusitis. J Clin Microbiol. 2021 Aug 18;JCM0095521. This retrospective study compared the performance of broad-range fungal to traditional methods including culture, direct stain, and intraoperative frozen section pathology in a cohort of 52 patients evaluated for invasive fungal sinusitis, including 34 (65%) with proven/probable invasive fungal disease. PCR and culture combined offered superior sensitivity (90%) compared to either PCR alone (85%) or culture alone (67.5%). Molecular methods were significantly more sensitive and specific than staining methods. PCR had equivalent sensitivity on FFPE and fresh tissue (42% vs 35%, p > 0.05) and had faster turnaround time than culture.

4. Gomez CA, Budvytiene I, Zemek AJ, Banaei N. Performance of targeted fungal sequencing for culture-independent diagnosis of invasive fungal disease. Clin Infect Dis. 2017;65(12):2035–41.

5. •• Senchyna F, Hogan CA, Murugesan K, Moreno A, Ho DY, Subramanian A, et al. Clinical accuracy and impact of plasma cell-free DNA fungal polymerase chain reaction panel for noninvasive diagnosis of fungal infection. Clin Infect Dis. 2021;73(9):1677–84. This study demonstrated how to implement a multi-target PCR amplification of multiple fungal targets from the cell-free DNA plasma fraction and evaluated assay performance. Sensitivity was 56.5–69% and specificity was >99% with median turnaround time of 3 days. These results suggest real-world utility as a non-invasive diagnostic tool.

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