Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units

Themoula Charalampous, Adela Alcolea-Medina, Luke B. Snell, Tom G.S. Williams, Rahul Batra, Christopher Alder, Andrea Telatin, Luigi Camporota, Christopher I.S. Meadows, Duncan Wyncoll, Nicholas A. Barrett, Carolyn J. Hemsley, Lisa Bryan, William Newsholme, Sara E. Boyd, Anna Green, Ula Mahadeva, Amita Patel, Penelope R. Cliff, Andrew J. PageJustin O’Grady, Jonathan D. Edgeworth*

*Corresponding author for this work

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23 Citations (Scopus)


Background: Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. Methods: CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. Results: An 8-h CMg workflow was 92% sensitive (95% CI, 75–99%) and 82% specific (95% CI, 57–96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of β-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. Conclusion: CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.

Original languageEnglish
Article number182
JournalGenome medicine
Issue number1
Early online date17 Nov 2021
Publication statusPublished - Dec 2021

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