Improving the diagnosis and management of serious infection using nanopore metagenomic sequencing

Abstract
Rapid and accurate diagnosis is critical for the effective treat- ment of life threatening infections, such as bloodstream, respiratory tract and complicated urinary tract infections. These clinical syn- dromes have complex aetiology and require the recognition of pathogens within challenging sample matrices. The “gold standard” culture techniques are labour intensive, have long turn-around times (≥2 days) and often offer poor clinical sensitivity. In the absence of rapidly available pathogen or resistance information, the patient is treated empirically with broad spectrum therapy. This empirical therapy is often unnecessarily potent or, conversely, sometimes ineffective due to inherent or acquired resistance.
A paradigm shift in diagnostics technology is required, to allow the development of a universal diagnostic which can detect any pathogen or resistance. Shotgun metagenomics sequencing has the potential to drive this shift by combining rapidity with compre- hensiveness beyond that of culture or PCR. Nanopore real-time sequencing technology has, for the first time, made it feasible to apply metagenomic sequencing to acute infection diagnosis.
By providing rapid pathogen identification and AMR profiling, metagenomic sequencing will afford clinicians with a timely and comprehensive diagnosis, reducing empiric treatment to a single dose and enabling tailored antimicrobial therapy. I will discuss our ongoing research on the development of metagenomic sequencing based diagnostic tests for bloodstream, urinary tract and respira- tory tract infections.
http://dx.doi.org/10.1016/j.bdq.2017.02.053