Please use this identifier to cite or link to this item: https://dora.health.qld.gov.au/qldresearchjspui/handle/1/10926
Title: Clinical implementation of routine whole-genome sequencing for hospital infection control of multi-drug resistant pathogens
Authors: Forde, Brian
Bergh, Haakon
Cuddihy, Thom
Hajkowicz, Krispin 
Hurst, Trish
Playford, E. Geoffrey
Henderson. Belinda C.
Runnegar, Naomi 
Clark, Julia 
Jennison, Amy 
Moss, Susan
Hume, Anna
Leroux, Hugo
Beatson, Scott A
Paterson, David L
Harris, Patrick NA
Issue Date: 3-May-2022
Publisher: Cold Spring Harbor Laboratory
Source: Clin Infect Dis., vol 76, issue 3, 1 Feb 2023
Journal: Clinical Infectious Diseases
Abstract: Background: Prospective whole-genome sequencing (WGS)-based surveillance may be the optimal approach to rapidly identify transmission of multi-drug resistant (MDR) bacteria in the healthcare setting. Methods: We prospectively collected methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Acinetobacter baumannii (CRAB), extended-spectrum beta-lactamase (ESBL-E), and carbapenemase-producing Enterobacterales (CPE) isolated from blood cultures, sterile sites, or screening specimens across three large tertiary referral hospitals (2 adult, 1 paediatric) in Brisbane, Australia. WGS was used to determine in silico multi-locus sequence typing (MLST) and resistance gene profiling via a bespoke genomic analysis pipeline. Putative transmission events were identified by comparison of core genome single nucleotide polymorphisms (SNPs). Relevant clinical meta-data were combined with genomic analyses via customised automation, collated into hospital-specific reports regularly distributed to infection control teams. Results: Over 4 years (April 2017 to July 2021) 2660 isolates were sequenced. This included MDR gram-negative bacilli (n = 293 CPE, n = 1309 ESBL), MRSA (n = 620), and VRE (n = 433). A total of 379 clinical reports were issued. Core genome SNP data identified that 33% of isolates formed 76 distinct clusters. Of the 76 clusters, 43 were contained to the 3 target hospitals, suggesting ongoing transmission within the clinical environment. The remaining 33 clusters represented possible inter-hospital transmission events or strains circulating in the community. In 1 hospital, proven negligible transmission of non-multi-resistant MRSA enabled changes to infection control policy. Conclusions: Implementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.
Description: Acknowledgments. The authors thank the scientists at Pathology Queensland and Forensic and Scientific Services for their assistance in the laboratory work and the infection control teams at the participating hospitals for their involvement and clinical input. Data availability. All genomes derived from this project are publicly available at NCBI Bioproject PRJNA797179: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA797179. Supplementary Data: Supplementary Table 1 (clinical meta-data) and Supplementary Table 2 (antimicrobial resistance genes) can be accessed via Harvard Dataverse (https://doi.org/10.7910/DVN/NOUWZY). Ethics. Ethical oversight was provided by The Forensic and Scientific Services Human Ethics Committee (reference HEC17_17) as a Low and Negligible Risk approval, with provision for a waiver of individual patient consent. Financial support. This work was supported by funding from the Queensland Genomics Health Alliance (now Queensland Genomics), Queensland Health, the Queensland Government. P. N. A. H. was supported by a National Health and Medical Research Council Early Career Fellowship Grant (grant number GNT1157530).
DOI: 10.1101/2022.05.02.22273921
10.1093/cid/ciac726
metadata.dc.rights.holder: Jennison, Amy
Keywords: Methicillin-Resistant Staphylococcus aureus;healthcare-associated infections;whole genome sequencing;clinical implementation;infection prevention and control;Multilocus Sequence Typing;Anti-Bacterial Agents
Type: Journal article
Appears in Sites:Forensic and Scientific Services Publications
Queensland Health Publications

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