Metagenomic sequencing detects respiratory pathogens in hematopoietic cellular transplant patients

Rationale: Current microbiologic diagnostics often fail to identify the etiology of lower respiratory tract infections (LRTI) in hematopoietic cellular transplant recipients (HCT), which precludes the implementation of targeted therapies. Objectives: To address the need for improved LRTI diagnostics, we evaluated the utility of metagenomic next generation sequencing (mNGS) of bronchoalveolar lavage (BAL) to detect microbial pathogens in HCT patients with acute respiratory illnesses. Methods: We enrolled 22 post-HCT adults ages 19-69 years with acute respiratory illnesses who underwent BAL at the University of Michigan between January 2012 and May 2013. mNGS was performed on BAL fluid to detect microbes and simultaneously assess the host transcriptional response. Results were compared against conventional microbiologic assays. Measurements and Main Results: Standard of care clinical diagnostics identified microbes in seven patients (32%), six of which were considered pathogens by tre...