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

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. 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. 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. 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.