Respiratory and blood samples metagenomic sequencing in diagnosing pulmonary infections in hematologic patients.

BACKGROUND

Bacterial and fungal pulmonary infections (BFPI) are common in hematological patients and pose significant diagnostic challenges. Metagenomic next-generation sequencing (mNGS) is valuable for diagnosing BFPI. However, for hematological patients with limited access to lower respiratory tract samples (LRTS), the clinical value of blood-mNGS compared to LRTS-mNGS requires further investigation.

METHODS

A retrospective analysis was conducted on 160 cases with suspected pneumonia who underwent both blood-mNGS and LRTS-mNGS within one week. Diagnostic performance and impacts on antimicrobial adjustments were evaluated using clinical composite diagnosis (CCD) as the reference.

RESULTS

Compared to CCD, LRTS-mNGS showed significantly higher positive percent agreement (PPA) than blood-mNGS [93.7% (119/127) vs. 34.6% (44/127), P < 0.001], with negative percent agreements (NPA) of 87.5% (21/24) and 91.7% (22/24), respectively. Blood-mNGS showed higher PPA in neutropenic than non-neutropenic patients [56.8% (21/37) vs. 25.6% (23/90), P = 0.001], with unique fungal detection advantages, identifying additional fungi in 7 cases: Mucorales (3), Aspergillus spp. (2), both Mucorales and Aspergillus spp. (1), and Pneumocystis spp. (1). Resistance genes were detected only by LRTS-mNGS. mNGS positively influenced antimicrobial adjustments in 54.3% (69/127) of cases, particularly for pathogens with low empirical coverage, such as Legionella spp. (0.0%, 0/7), Pneumocystis spp. (52.4%, 11/21), and Mucorales (55.6%, 5/9). Blood-mNGS detected these pathogens at rates of 71.4% (5/7), 23.8% (5/21), and 77.8% (7/9), respectively.

CONCLUSION

LRTS-mNGS outperformed blood-mNGS in diagnostic performance and resistance detection. Blood-mNGS identified pathogens in one-third of BFPI cases, with value for certain fungal infections, especially in hematologic patients with limited LRTS access. TRIAL REGISTRATION: Not applicable. This study is a retrospective analysis and does not require clinical trial registration.