Metagenomics to Assist in the Diagnosis of Bloodstream Infection.

Abstract

Metagenomic next-generation sequencing (mNGS) has emerged as a promising technology that enables pan-pathogen detection from any source. However, clinical utility and practical integration into the clinical microbiology work flow and a bloodstream infection detection algorithm are currently uncharted. In the context of bloodstream infections, the challenges associated with blood culture, including sensitivity, postantibiotic treatment, attaining sufficient volumes sufficient volumes, and turnaround time, are well-known. Molecular assays have helped expedite turnaround time, especially when performed directly from positive culture media bottles. mNGS offers an unbiased but more complex version of molecular testing directly from sample, but it is unclear how and if it should be implemented in the clinical microbiology laboratory today. Here we map out the potential utility and application of mNGS tests to infectious disease diagnostics from blood sources, including intrinsic limitations of the methodology in diagnosing bloodstream infections and sepsis vs DNAemia, current barriers to integration into routine workup, and milestones that may need to be met before implementation. Polymerases and pores move faster than bugs divide, so the thermodynamics of mNGS adoption for bloodstream infection is favorable. Nonetheless, considerable activation barriers exist that will slow this likely diagnostic transition. We eagerly await the manufacturer who designs an integrated sample-to-answer box to do for mNGS what has been done for other aspects of molecular detection.