Detection of Pneumonia Pathogens from Plasma Cell-Free DNA

We conducted unbiased metagenomic next-generation sequencing (mNGS) of paired plasma and respiratory fluid from 25 subjects, 18 with pneumonia (four with concurrent bloodstream infections) and seven with non-infectious respiratory illnesses. Cell-free plasma mNGS identified one or more culture-confirmed bacterial or fungal pathogens in 72% of patients with pneumonia, compared to 100% for respiratory mNGS. In two patients who developed probable ventilator-associated pneumonia (VAP), plasma mNGS afforded early detection of the eventual culture-confirmed VAP pathogens. Our findings suggest that in a majority of patients with severe pneumonia, circulating microbial DNA from confirmed respiratory pathogens can be detected in the bloodstream, even in the setting of negative blood cultures.