Genomics for Molecular Epidemiology and Detecting Transmission of Carbapenemase-Producing Enterobacterales in Victoria, Australia, 2012 to 2016

Norelle L Sherry; Courtney R Lane; Jason C Kwong; Mark Schultz; Michelle Sait; Kerrie Stevens; Susan Ballard; Anders Gonçalves da Silva; Torsten Seemann; Claire L Gorrie; Timothy P Stinear; Deborah A Williamson; Judith Brett; Annaliese van Diemen; Marion Easton; Benjamin P Howden

doi:10.1128/JCM.00573-19

Genomics for Molecular Epidemiology and Detecting Transmission of Carbapenemase-Producing Enterobacterales in Victoria, Australia, 2012 to 2016

J Clin Microbiol. 2019 Aug 26;57(9):e00573-19. doi: 10.1128/JCM.00573-19. Print 2019 Sep.

Authors

Norelle L Sherry^{1

2}, Courtney R Lane^{1

3}, Jason C Kwong^{1

2

4}, Mark Schultz^{1

4}, Michelle Sait¹, Kerrie Stevens¹, Susan Ballard¹, Anders Gonçalves da Silva^{1

4}, Torsten Seemann^{1

4}, Claire L Gorrie^{1

4}, Timothy P Stinear⁴, Deborah A Williamson^{1

4}, Judith Brett⁵, Annaliese van Diemen³, Marion Easton³, Benjamin P Howden^{6

2

4}

Affiliations

¹ Antimicrobial Reference and Research Unit, Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia.
² Department of Infectious Diseases, Austin Health, Heidelberg, Australia.
³ Health Protection Branch, Department of Health and Human Services, Victorian State Government, Melbourne, Australia.
⁴ Doherty Applied Microbial Genomics, Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia.
⁵ Victorian Healthcare Associated Infection Surveillance Coordinating Centre, Melbourne, Australia.
⁶ Antimicrobial Reference and Research Unit, Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection & Immunity, Melbourne, Australia bhowden@unimelb.edu.au.

Abstract

Carbapenemase-producing Enterobacterales (CPE) are being increasingly reported in Australia, and integrated clinical and genomic surveillance is critical to effectively manage this threat. We sought to systematically characterize CPE in Victoria, Australia, from 2012 to 2016. Suspected CPE were referred to the state public health laboratory in Victoria, Australia, from 2012 to 2016 and examined using phenotypic, multiplex PCR and whole-genome sequencing (WGS) methods and compared with epidemiological metadata. Carbapenemase genes were detected in 361 isolates from 291 patients (30.8% of suspected CPE isolates), mostly from urine (42.1%) or screening samples (34.8%). IMP-4 (28.0% of patients), KPC-2 (25.3%), NDM (24.1%), and OXA carbapenemases (22.0%) were most common. Klebsiella pneumoniae (48.8% of patients) and Escherichia coli (26.1%) were the dominant species. Carbapenemase-inactivation method (CIM) testing reliably detected carbapenemase-positive isolates (100% sensitivity, 96.9% specificity), identifying an additional five CPE among 159 PCR-negative isolates (IMI and SME carbapenemases). When epidemiologic investigations were performed, all pairs of patients designated "highly likely" or "possible" local transmission had ≤23 pairwise single-nucleotide polymorphisms (SNPs) by genomic transmission analysis; conversely, all patient pairs designated "highly unlikely" local transmission had ≥26 pairwise SNPs. Using this proposed threshold, possible local transmission was identified involving a further 16 patients for whom epidemiologic data were unavailable. Systematic application of genomics has uncovered the emergence of polyclonal CPE as a significant threat in Australia, providing important insights to inform local public health guidelines and interventions. Using our workflow, pairwise SNP distances between CPE isolates of ≤23 SNPs suggest local transmission.

Keywords: Enterobacterales; Enterobacteriaceae; antimicrobial resistance; carbapenemase; epidemiologic surveillance; molecular epidemiology; whole-genome sequencing.

Publication types

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

MeSH terms

Aged
Bacterial Proteins / genetics
Bacteriological Techniques
Carbapenem-Resistant Enterobacteriaceae / classification
Carbapenem-Resistant Enterobacteriaceae / genetics
Carbapenem-Resistant Enterobacteriaceae / isolation & purification*
Disease Transmission, Infectious*
Enterobacteriaceae Infections / microbiology
Enterobacteriaceae Infections / transmission*
Female
Humans
Male
Middle Aged
Molecular Diagnostic Techniques / methods*
Molecular Epidemiology / methods*
Molecular Typing / methods
Multiplex Polymerase Chain Reaction
Victoria
Whole Genome Sequencing
beta-Lactamases / genetics

Substances

Bacterial Proteins
beta-Lactamases
carbapenemase