CAS9-mNGS Detects Antimicrobial Resistant Pathogens

Antimicrobial resistance (AMR) is a known challenge to human health that increasingly leads to treatment failure in patients with lower respiratory tract infections (LRTI). In this study, the recently described culture-independent method for LRTI diagnosis, metagenomic next generation sequencing (mNGS), was optimized for detection and surveillance of AMR pathogens in critically ill adults with acute respiratory failure. RNA-sequencing coupled with CRISPR/Cas9-enriched mNGS allowed rapid detection of AMR genes with high sensitivity using an Oxford nanopore platform, highlighting the future potential for point of care diagnosis. Modeled impact of an estimated 24-hour turnaround time on antimicrobial stewardship demonstrates the potential to significantly reduce use of inappropriate antimicrobials and enhance epidemiologic surveillance of AMR pathogens.