Clinical Implementation of Routine Whole-genome Sequencing for Hospital Infection Control of Multi-drug Resistant Pathogens.

clinical implementation healthcare-associated infections infection prevention and control multi-resistant organisms whole genome sequencing

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
08 02 2023
Historique:
received: 10 05 2022
pubmed: 4 9 2022
medline: 11 2 2023
entrez: 3 9 2022
Statut: ppublish

Résumé

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. 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. 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. Implementation of routine WGS for MDR pathogens in clinical laboratories is feasible and can enable targeted infection prevention and control interventions.

Sections du résumé

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.

Identifiants

pubmed: 36056896
pii: 6691363
doi: 10.1093/cid/ciac726
doi:

Substances chimiques

Anti-Bacterial Agents 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1277-e1284

Informations de copyright

© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Déclaration de conflit d'intérêts

Potential conflicts of interest. P. N. A. H. reports research grants from Merck, Sandoz, and Shionogi, outside the submitted work; has served on advisory boards for Sandoz and Merck, and has received speaker's fees from Pfizer, Sandoz, and Sumitomo. D. L. P reports research grants from Merck, Pfizer, and Shionogi outside the submitted work; has received honoraria for advisory board membership from Merck, Pfizer, Shionogi, GSK, QPex, Entasis, VenatoRx, BioMerieux, and Accelerate. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Auteurs

Brian M Forde (BM)

Faculty of Medicine, UQ Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia.

Haakon Bergh (H)

Central Microbiology, Pathology Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.

Thom Cuddihy (T)

Faculty of Medicine, UQ Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia.

Krispin Hajkowicz (K)

Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.

Trish Hurst (T)

Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.

E Geoffrey Playford (EG)

Infection Management Services, Princess Alexandra Hospital, Metro South Hospital and Health Service, Brisbane, QLD, Australia.

Belinda C Henderson (BC)

Infection Management Services, Princess Alexandra Hospital, Metro South Hospital and Health Service, Brisbane, QLD, Australia.

Naomi Runnegar (N)

Infection Management Services, Princess Alexandra Hospital, Metro South Hospital and Health Service, Brisbane, QLD, Australia.
Faculty of Medicine, PA-Southside Clinical School, University of Queensland, Brisbane, QLD, Australia.

Julia Clark (J)

Infection Management and Prevention Service, Queensland Children's Hospital, Brisbane, QLD, Australia.
Centre for Children's Health Research, Children's Health Queensland, Brisbane, Australia.

Amy V Jennison (AV)

Public Health Microbiology, Forensic and Scientific Services, Queensland Health, Brisbane, QLD, Australia.

Susan Moss (S)

Public Health Microbiology, Forensic and Scientific Services, Queensland Health, Brisbane, QLD, Australia.

Anna Hume (A)

Central Microbiology, Pathology Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.
Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.

Hugo Leroux (H)

Australian e-Health Research Centre, CSIRO, Brisbane, QLD, Australia.

Scott A Beatson (SA)

School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD, Australia.

David L Paterson (DL)

Faculty of Medicine, UQ Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia.
Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Herston, QLD, Australia.

Patrick N A Harris (PNA)

Faculty of Medicine, UQ Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia.
Central Microbiology, Pathology Queensland, Royal Brisbane & Women's Hospital, Brisbane, QLD, Australia.

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