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

## TL;DR

This study compares metagenomic sequencing with traditional methods for diagnosing lung infections in cancer patients, finding that sequencing detects more pathogens but needs more validation.

## Contribution

The study introduces metagenomic sequencing as a potential diagnostic tool for pulmonary infections in hematologic malignancy patients.

## Key findings

- Metagenomic sequencing identified additional plausible pathogens in over half of patients.
- Sequencing showed modest agreement with conventional testing for bacterial infections.
- Fungal pathogen detection was poor with sequencing methods.

## Abstract

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.

How does metagenomic sequencing of the lower respiratory tract compare with conventional microbiologic testing among patients with hematologic malignancy?

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.

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.

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.