Discussion

These cases, which represent the first use of real-time metagenomic sequencing to identify pathogens in pneumonia, demonstrate the enormous potential of rapid sequencing-based techniques to accelerate and improve our diagnosis and management of this common and lethal disease. We here demonstrate that in principle, a real-time metagenomic approach using currently available tools is capable of identifying pathogens faster than conventional in-use culture-based techniques. An acceleration in pathogen identification in pneumonia holds promise to improve our delivery of tailored antimicrobial therapy, improving patient outcomes and facilitating antimicrobial stewardship by minimizing the need for broad, empiric antimicrobial coverage. In addition to accelerating time to diagnosis of culturable pathogens, real-time metagenomics holds potential to identify pathogens that cannot be grown in culture. Unlike polymerase chain reaction (PCR)-based and 16S ribosomal RNA gene-based sequencing approaches, a metagenomic approach is “agnostic” regarding the taxonomy of pathogens and can identify bacteria, viruses, and fungi alike. This sequencing platform has proven capable of identifying RNA viruses in nonlung specimens (5, 6), demonstrating its potential for an impressive breadth of taxonomic detection. Thus, a real-time