Multi-site implementation of whole genome sequencing for hospital infection control: A prospective genomic epidemiological analysis

Norelle L Sherry; Claire L Gorrie; Jason C Kwong; Charlie Higgs; Rhonda L Stuart; Caroline Marshall; Susan A Ballard; Michelle Sait; Tony M Korman; Monica A Slavin; Robyn S Lee; Maryza Graham; Marcel Leroi; Leon J Worth; Hiu Tat Chan; Torsten Seemann; M Lindsay Grayson; Benjamin P Howden; Controlling Superbugs Study Group

doi:10.1016/j.lanwpc.2022.100446

Multi-site implementation of whole genome sequencing for hospital infection control: A prospective genomic epidemiological analysis

Lancet Reg Health West Pac. 2022 Apr 12:23:100446. doi: 10.1016/j.lanwpc.2022.100446. eCollection 2022 Jun.

Authors

Norelle L Sherry^{1

2

3}, Claire L Gorrie^{1

3}, Jason C Kwong^{2

3

4}, Charlie Higgs³, Rhonda L Stuart^{5

6

7}, Caroline Marshall^{8

9}, Susan A Ballard¹, Michelle Sait¹, Tony M Korman^{5

6

10}, Monica A Slavin^{11

12}, Robyn S Lee³, Maryza Graham^{5

6

10}, Marcel Leroi^{2

13}, Leon J Worth^{11

12}, Hiu Tat Chan¹⁴, Torsten Seemann^{1

3}, M Lindsay Grayson^{2

4

13}, Benjamin P Howden^{1

2

3}; Controlling Superbugs Study Group

Affiliations

¹ Microbiological Diagnostic Unit (MDU) Public Health Laboratory, Department of Microbiology & Immunology at the Peter Doherty Institute for Infection & Immunity, University of Melbourne, Melbourne, Victoria, Australia.
² Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia.
³ Department of Microbiology & Immunology at the Peter Doherty Institute for Infection & Immunity, University of Melbourne, Melbourne, Victoria, Australia.
⁴ Department of Medicine, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
⁵ Monash Infectious Diseases, Monash Health, Clayton, Victoria, Australia.
⁶ Monash University, Clayton, Victoria, Australia.
⁷ South East Public Health Unit, Monash Health, Clayton, Victoria, Australia.
⁸ Infection Prevention & Surveillance, Victorian Infectious Diseases Service, Melbourne Health, Parkville, Victoria, Australia.
⁹ Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Victoria, Australia.
¹⁰ Department of Microbiology, Monash Health, Clayton, Victoria, Australia.
¹¹ Department of Infectious Diseases, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
¹² National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.
¹³ Department of Microbiology, Austin Health, University of Melbourne, Heidelberg, Victoria, Australia.
¹⁴ Department of Microbiology, Melbourne Health, Parkville, Victoria, Australia.

Abstract

Background: Current microbiological methods lack the resolution to accurately identify multidrug-resistant organism (MDRO) transmission, however, whole genome sequencing can identify highly-related patient isolates providing opportunities for precision infection control interventions. We investigated the feasibility and potential impact of a prospective multi-centre genomics workflow for hospital infection control.

Methods: We conducted a prospective genomics implementation study across eight Australian hospitals over 15 months (2017,2018), collecting all clinical and screening isolates from inpatients with vanA VRE, MRSA, ESBL Escherichia coli (ESBL-Ec), or ESBL Klebsiella pneumoniae (ESBL-Kp). Genomic and epidemiologic data were integrated to assess MDRO transmission.

Findings: In total, 2275 isolates were included from 1970 patients, predominantly ESBL-Ec (40·8%) followed by MRSA (35·6%), vanA VRE (15·2%), and ESBL-Kp (8·3%).Overall, hospital and genomic epidemiology showed 607 patients (30·8%) acquired their MDRO in hospital, including the majority of vanA VRE (266 patients, 86·4%), with lower proportions of ESBL-Ec (186 patients, 23·0%), ESBL-Kp (42 patients, 26·3%), and MRSA (113 patients, 16·3%). Complex patient movements meant the majority of MDRO transmissions would remain undetected without genomic data.The genomics implementation had major impacts, identifying unexpected MDRO transmissions prompting new infection control interventions, and contributing to vanA VRE becoming a notifiable condition. We identified barriers to implementation and recommend strategies for mitigation.

Interpretation: Implementation of a multi-centre genomics-informed infection control workflow is feasible and identifies many unrecognised MDRO transmissions. This provides critical opportunities for interventions to improve patient safety in hospitals.

Funding: Melbourne Genomics Health Alliance (supported by State Government of Victoria, Australia), and National Health and Medical Research Council (Australia).

Keywords: Antimicrobial resistance; ESBL-Ec, Extended-spectrum beta-lactamase Escherichia coli; ESBL-Kp, Extended-spectrum beta-lactamase Klebsiella pneumoniae; Hospital epidemiology; Infection prevention and control; MDRO, Multidrug-resistant organism; MRSA, Methicillin-resistant Staphylococcus aureus; VRE, Vancomycin-resistant Enterococcus; WGS, Whole genome sequencing; Whole genome sequencing.