Aspergillus fumigatus in mechanically ventilated pneumonia- independent mortality risk and synergistic microbiome signatures from a multicenter mNGS cohort.

AIM OF THE STUDY: Invasive aspergillosis is a life-threatening complication in mechanically ventilated patients with pneumonia, predominantly caused by Aspergillus fumigatus. However, its independent mortality risk and early-warning strategies in critically ill populations remain unclear. METHODS: In this multicenter retrospective cohort study, we enrolled 1567 mechanically ventilated patients with severe pneumonia who underwent bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) across 12 tertiary hospitals in China (January 2019–March 2023). Propensity score matching (1:1) balanced confounders, and Cox regression quantified the independent mortality risk of A. fumigatus infection. RESULTS: The A. fumigatus detection rate was 10.27% (161/1567). Post-matching, 28-day mortality was significantly higher in A. fumigatus-positive versus negative cohorts (66% vs 47%, p = 0.001). Multivariable analysis confirmed A. fumigatus as an independent mortality risk factor (HR = 1.79, 95%CI 1.49–2.17, p < 0.001), with significant associations to underlying renal disease (19% vs 12%, p = 0.005), connective tissue disease (7% vs 4%, p = 0.026), and multi-organ dysfunction (ep < 0.05). Microbial community analysis revealed co-colonization synergies with Enterococcus faecium, Enterococcus faecalis, Candida albicans, HSV-1, and EBV. CONCLUSIONS: A. fumigatus infection independently increases 28-day mortality risk in mechanically ventilated patients. Early intensified screening and intervention are warranted for individuals with ≥ 3 organ dysfunctions, underlying renal/connective tissue diseases, or respiratory co-colonization by synergistic microbes.