The clinical application of metagenomic next-generation sequencing for invasive pulmonary aspergillosis in neutropenic patients: a multicenter retrospective study in the ICU.

BACKGROUND

Early initiation of targeted antifungal therapy is critical for improving outcomes in neutropenic patients with invasive pulmonary aspergillosis (IPA) in the intensive care unit (ICU). Although metagenomic next-generation sequencing (mNGS) is valuable for pathogen detection, its clinical value in IPA patients with neutropenia remains unclear.

METHODS

This multicenter retrospective study included patients clinically diagnosed with invasive pulmonary aspergillosis (IPA). All patients underwent both conventional microbiological tests (CMTs) and metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). Based on neutrophil status, patients were stratified into neutropenic and non-neutropenic groups and further divided into mNGS-guided and CMT-guided groups according to the antifungal treatment strategy.

RESULTS

mNGS demonstrated higher pathogen detection rate than conventional microbiological tests (CMTs) in both neutropenic and non-neutropenic patients with invasive pulmonary aspergillosis (IPA). It also identified a broader pathogen spectrum and a higher proportion of mixed infections. Overall, IPA patients in the mNGS-guided group had lower 28-day mortality compared with the CMT-guided group (23.17% vs. 43.75%, P = 0.04). Multivariate analysis indicated that mNGS-guided therapy was associated with reduced 28-day mortality (adjusted OR = 0.329, 95% CI: 0.111-0.974, P = 0.045). A significant interaction between treatment strategy and neutrophil status was observed (adjusted P = 0.002). In subgroup analysis, the survival benefit of mNGS-guided therapy was mainly observed in neutropenic IPA patients, who achieved higher rates of appropriate antifungal therapy and lower mortality, whereas no significant intergroup difference was found among non-neutropenic IPA patients.

CONCLUSION

mNGS-guided antifungal therapy significantly reduced 28-day mortality in neutropenic IPA patients, whereas no clear effect was observed in non-neutropenic patients. These findings highlight the potential clinical value of mNGS in guiding antifungal therapy in neutropenic IPA patients.