Publication
Application of respiratory metagenomics for COVID-19 patients on the intensive care unit to inform appropriate initial antimicrobial treatment and rapid detection of nosocomial transmission
Publisher:
Cold Spring Harbor Laboratory
Date:
03-12-2020
DOI:
10.1101/2020.11.26.20229989
Abstract: Clinical metagenomics (CMg) is being evaluated for translation from a research tool into routine diagnostic service, but its potential to significantly improve management of acutely unwell patients has not been demonstrated. The SARS-CoV-2 pandemic provides impetus to determine that benefit given increased risk of secondary infection and nosocomial transmission by multi-drug resistant (MDR) pathogens linked with expansion of critical care capacity. Prospective evaluation of CMg using nanopore sequencing was performed on 43 respiratory s les over 14 weeks from a cohort of 274 intubated patients across seven COVID-19 intensive care units. Bacteria or fungi were cultured from 200 (73%) patients, with a predominance of Klebsiella spp . (31%) and C. striatum (7%) amongst other common respiratory pathogens. An 8 hour CMg workflow was 93% sensitive and 81% specific for bacterial identification compared to culture, and reported presence or absence of β-lactam resistance genes carried by Enterobacterales that would modify initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus (4 positive and 39 negative s les). Single nucleotide polymorphism (SNP)-typing using 24 hour sequence data identified an MDR- K. pneumoniae ST307 outbreak involving 4 patients and an MDR- C. striatum outbreak potentially involving 14 patients across three ICUs. CMg testing for ICU patients provides same-day pathogen detection and antibiotic resistance prediction that significantly improves initial treatment of nosocomial pneumonia and rapidly detects unsuspected outbreaks of MDR-pathogens.