Metagenomic next-generation sequencing for the diagnosis of suspected pneumonia in immunocompromised patients

Objectives : To evaluate the potential of metagenomic next-generation sequencing (mNGS), compared with that of comprehensive conventional microbiological tests (CMTs), of bronchoalveolar lavage fluid (BALF) as a front-line diagnostic for immunocompromised patients with suspected pneumonia. Methods : Sixty critically ill immunocompromised patients undergoing both mNGS of BALF and CMTs for suspected pneumonia were retrospectively analysed. The diagnostic performance was compared between mNGS and CMTs, using the composite diagnosis as the reference standard. Results : Forty-nine patients were diagnosed with microbiologically confirmed pneumonia, with 55% having polymicrobial infections. There was no significant difference in the overall diagnostic accuracy between mNGS and CMTs (61.7% vs 76.7%; P = 0.11). mNGS and CMTs had comparable diagnostic accuracy for bacterial and viral infections. Although mNGS identified more viral pneumonia, it had a much lower diagnostic accuracy for fungal infections (76.7% vs 99.2%; P < 0.001), mainly due to the low sensitivity for invasive pulmonary aspergillosis (45.5% vs 100%; P < 0.001). Conclusion : The overall diagnostic performance of BALF mNGS as a first-line diagnostic was similar to that of comprehensive CMTs, except in the case of a lack of consideration of potential pathogens or limited CMTs. The combination of mNGS and CMTs may be the best diagnostic strategy.