Translating genomics into practice for real-time surveillance and response to carbapenemase-producing Enterobacteriaceae: Evidence from a complex multi-institutional KPC outbreak

Jason C. Kwong, Courtney R. Lane, Finn Romanes, Anders Gonçalves da Silva, Marion Easton, Katie Cronin, Mary Jo Waters, Takehiro Tomita, Kerrie Stevens, Mark B. Schultz, Sarah L. Baines, Norelle L. Sherry, Glen P. Carter, Andre Mu, Michelle Sait, Susan A. Ballard, Torsten Seemann, Timothy P. Stinear, Benjamin P. Howden

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27 Citations (Scopus)

Abstract

Background: Until recently, Klebsiella pneumoniae carbapenemase (KPC)- producing Enterobacteriaceae were rarely identified in Australia. Following an increase in the number of incident cases across the state of Victoria, we undertook a real-time combined genomic and epidemiological investigation. The scope of this study included identifying risk factors and routes of transmission, and investigating the utility of genomics to enhance traditional field epidemiology for informing management of established widespread outbreaks. Methods: All KPC-producing Enterobacteriaceae isolates referred to the state reference laboratory from 2012 onwards were included. Whole-genome sequencing was performed in parallel with a detailed descriptive epidemiological investigation of each case, using Illumina sequencing on each isolate. This was complemented with PacBio long-read sequencing on selected isolates to establish high-quality reference sequences and interrogate characteristics of KPC-encoding plasmids. Results: Initial investigations indicated that the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates (K. pneumoniae 92%) identified from 35 different locations across metropolitan and rural Victoria between 2012 and 2015. Initial combined analyses of the epidemiological and genomic data resolved the outbreak into distinct nosocomial transmission networks, and identified healthcare facilities at the epicentre of KPC transmission. New cases were assigned to transmission networks in real-time, allowing focussed infection control efforts. PacBio sequencing confirmed a secondary transmission network arising from interspecies plasmid transmission. Insights from Bayesian transmission inference and analyses of within-host diversity informed the development of state-wide public health and infection control guidelines, including interventions such as an intensive approach to screening contacts following new case detection to minimise unrecognised colonisation. Conclusion: A real-time combined epidemiological and genomic investigation proved critical to identifying and defining multiple transmission networks of KPC Enterobacteriaceae, while data from either investigation alone were inconclusive. The investigation was fundamental to informing infection control measures in realtime and the development of state-wide public health guidelines on carbapenemaseproducing Enterobacteriaceae surveillance and management.

Original languageEnglish
Article numbere4210
Number of pages32
JournalPeerJ
Volume2018
Issue number1
DOIs
Publication statusPublished - 3 Jan 2018
Externally publishedYes

Keywords

  • Antimicrobial resistance
  • Klebsiella pneumoniae carbapenemase
  • Microbial genomics
  • Multidrugresistant organisms
  • Outbreak investigation
  • Transmission modelling
  • Whole-genome sequencing

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