Abstract
The clinical utility of metagenomic next-generation sequencing (mNGS) in immunocompromised critically ill patients with invasive pulmonary aspergillosis (IPA) remains poorly studied. Given the diagnostic challenges and high mortality associated with IPA in this population, further research on the use of mNGS for early diagnosis and targeted therapy is urgently needed. This multicenter, retrospective, observational study enrolled immunocompromised patients admitted to the intensive care units of six tertiary hospitals in China from April 2021 to November 2024. Comprehensive clinical data were systematically collected, including demographic information, underlying conditions, and detailed records of specimen types and microbiological examination methods. The primary objective was to evaluate the diagnostic and prognostic values of mNGS in comparison to conventional microbiological tests (CMTs) for IPA in this high-risk population. Kappa analysis results indicated a significant agreement between the results of mNGS and CMTs in both groups (Kappa value = 0.638, P < 0.001). The receiver operating curve demonstrated that mNGS exhibited comparable sensitivity (94.03% vs. 95.52%) and higher specificity (96.20% vs. 78.85%), as well as a higher area under the curve (AUC) (0.951 vs. 0.872) in diagnosing IPA compared to CMTs. Moreover, mNGS was significantly superior to other single methods, including cultures (AUC: 0.620, sensitivity: 27.88%, specificity: 96.15%), galactomannan test (AUC: 0.711, sensitivity: 53.73%, specificity: 88.46%), and PCR (AUC: 0.770, sensitivity: 62.69%, specificity: 91.35%). The clinical application of mNGS-guided antibiotic adjustments significantly decreased the 28-day mortality rate (46.51% vs. 66.67%, P < 0.05). mNGS is a feasible and highly sensitive diagnostic tool for detecting Aspergillus infections in immunocompromised critically ill patients compared to CMTs and other single conventional methods. It also performs well in identifying mixed infections, facilitating appropriate antibiotic regimen adjustments and improving patient prognosis. IMPORTANCE: mNGS demonstrated significantly higher specificity and area under the curve for diagnosing IPA in immunocompromised critically ill patients compared to CMTs. mNGS showed superior diagnostic performance over single methods, such as cultures, galactomannan test, and PCR, with higher sensitivity and specificity for Aspergillus detection. The use of mNGS-guided antibiotic adjustments led to a significant reduction in 28-day mortality (46.51% vs. 66.67%) among immunocompromised patients. mNGS demonstrated utility in identifying mixed infections, supporting targeted therapy and better patient outcomes. The application of mNGS in diagnosing IPA and guiding treatment in ICU patients helped optimize antibiotic regimens, ultimately improving clinical prognosis.