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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

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 carbapenemasepositive 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.

Original languageEnglish
Article numbere00573-19
JournalJournal of Clinical Microbiology
Volume57
Issue number9
DOIs
Publication statusPublished - 2019
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords

  • Antimicrobial resistance
  • Carbapenemase
  • Enterobacterales
  • Enterobacteriaceae
  • Epidemiologic surveillance
  • Molecular epidemiology
  • Whole-genome sequencing

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