Rapid Metagenomic Sequencing of Bronchoalveolar Lavage Fluid for Diagnosis of Infection in Patients With Hematologic Malignancies and Pulmonary Complications

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BACKGROUND: Diagnosing pulmonary complications (PCs) in hematologic malignancies remains challenging due to insensitive conventional microbiologic testing (CMT) and overlapping clinical manifestations of infectious and noninfectious pulmonary complications. For these reasons, empirical antimicrobials and immunosuppression (eg, corticosteroids) are used for prolonged periods. RESEARCH QUESTION: How does metagenomic sequencing of the lower respiratory tract compare with conventional microbiologic testing among patients with hematologic malignancy? STUDY DESIGN AND METHODS: Prospective proof-of-concept cohort study of 30 adult in-patients with hematologic malignancies and PCs who underwent bronchoscopy for suspected lower respiratory tract infection. RESULTS: CMT identified a pathogen via culture- or polymerase chain reaction-based testing in 53% of patients. 16S sequencing demonstrated 66.7% positive and 42.9% negative concordance with CMT, while also identifying additional plausible respiratory pathogens in 59.3% of patients. Nanopore demonstrated 6.7% positive and 87.5% negative concordance with CMT and identified additional plausible respiratory pathogens in 42.3% of patients. INTERPRETATION: Culture-independent sequencing approaches had modest agreement with CMT when considering bacterial PCs and showed poor detection of fungal pathogens. Sequencing frequently identified additional plausible respiratory pathogens, and further validation is needed to determine if such detection represents clinically missed infections or nonpathogenic colonization.

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