Diagnostic Value of Metagenomic Next-Generation Sequencing for Pulmonary Fungal Infections in Patients with Haematological Diseases: A Multicentre Retrospective Study.

Objectives

To evaluate the diagnostic value, clinical application and potential utility of metagenomic next-generation sequencing (mNGS) for pulmonary fungal infections (PFI) in patients with haematological diseases.

Methods

A total of 994 patients with haematological diseases and suspected pulmonary infection were included, comprising 514 bronchoalveolar lavage fluid (BALF)-mNGS and 499 peripheral blood (PB)-mNGS tests. Clinical characteristics, diagnostic performance, false-negative factors, antifungal treatment modification and outcomes were analysed.

Results

Based on the 2020 revised EORTC/ MSGERC criteria, 210 patients were classified as PFI, 156 as possible PFI and 628 as non-PFI. For BALF-mNGS, the diagnostic performance for PFI showed an AUC of 0.731, with a sensitivity of 72% and specificity of 74%. For PB-mNGS, the diagnostic performance for PFI showed an AUC of 0.717, with a sensitivity of 63% and specificity of 80%. Among the 156 patients classified as possible PFI (166 mNGS tests), fungi were detected by 130 tests (78.3%). Azole prophylaxis (OR, 2.42; P=0.038) were associated with false-negative mNGS results, whereas neutropenia was associated with fewer false-negative results (OR, 0.33; P=0.012). After mNGS reporting, antifungal therapy was modified in 312 patients (31.4%).

Conclusions

mNGS enhances fungal pathogen detection in high-risk haematological patients but should not be used as a standalone diagnostic test.