Enhanced Pathogen Detection in Hematology Patients with Respiratory Infections Using Targeted Next-Generation Sequencing (tNGS)

Background: Respiratory infections, involving both upper and lower respiratory tracts, represent a common and potentially life-threatening complication in patients with hematologic disorders. These patients exhibit compromised immunity and require highly sensitive diagnostic methods for both timing and capability. Traditional microbiological techniques often demonstrate inadequate diagnostic performance and delayed results, necessitating the exploration of alternative approaches. Methods: Sputum samples were collected from patients with hematologic diseases and concurrent respiratory infections (as the majority could not undergo bronchoalveolar lavage). The samples underwent Targeted Next-Generation Sequencing (tNGS), and the results were compared with those from traditional microbiological testing (TMT). The study aimed to evaluate the diagnostic performance, economic benefits, and pathogen prevalence—including fungi, viruses, atypical pathogens, and bacteria—along with the clinical impact of tNGS-guided treatment modifications. Results: tNGS demonstrated superior pathogen detection (98.6%) compared to TMT (47.2%), identifying bacteria in 79.7%, viruses in 87.8%, fungi in 58.1%, and atypical pathogens in 0.02% of cases. Common bacterial pathogens included Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, and Stenotrophomonas maltophilia. Predominant fungal pathogens included Aspergillus flavus, Aspergillus niger, Aspergillus fumigatus, and Candida glabrata, while viral pathogens included Epstein-Barr virus, novel coronavirus, Herpes simplex virus type 1, and rhinovirus type A. The mean turnaround time for tNGS was 24 hours, significantly faster than TMT (3–5 days), and tNGS proved more cost-effective. Treatment modifications based on tNGS results were implemented in 55.6% of cases. Conclusion: tNGS offers notable improvements in pathogen detection, especially for fungi and atypical pathogens, enabling timely, targeted antimicrobial therapy for immunocompromised hematologic malignancy patients. Additionally, tNGS demonstrates excellent cost-effectiveness, rapid result turnaround, and extensive pathogen coverage, emphasizing its potential to enhance clinical outcomes. These findings advocate for the integration of tNGS into clinical practice, particularly for hematologic patients requiring more precise diagnostic capabilities.