Abstract
BackgroundClinical 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.MethodsCMg 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.ResultsAn 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.ConclusionCMg 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.
Highlights
Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions
Clinical and microbiological characteristics of COVID-19 patients In total, 175 invasively ventilated COVID-19 patients were admitted to 7 intensive care unit (ICU), between 11 April and 15 June 2020, of which 34 patients with suspected secondary infection were chosen for inclusion in this CMg proof-ofconcept study and had one or more respiratory samples analysed by CMg (Table 1)
Respiratory pathogens cultured from CMg patients were representative of those found in the samples from the patient cohort over the 9-week period of the CMg study (Table 1) as well as with patients admitted across the 7 ICUs during the first wave from March to June 2020 (Additional file 1: Table S3)
Summary
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. The intensive care unit (ICU) is a dynamic environment with frequent staff-patient contact for invasive monitoring, interventions and personal care that together introduce the risk of secondary or nosocomial infection [1]. SARS-CoV-2 has put considerable strain on ICUs, due to the expansion of bed capacity with severely unwell patients, which has the potential to increase nosocomial infection, antimicrobial treatment and antimicrobial resistance (AMR). The COVID-19 pandemic re-enforces the need for rapid comprehensive diagnostics to improve antimicrobial stewardship and help prevent emergence and transmission of multi-drug-resistant (MDR) organisms
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