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Title: Translating genomics into practice for real-time surveillance and response to carbapenemase-producing Enterobacteriaceae: evidence from a complex multi-institutional KPC outbreak.
Austin Authors: Kwong, Jason C ;Lane, Courtney R;Romanes, Finn;Gonçalves da Silva, Anders;Easton, Marion;Cronin, Katie;Waters, Mary Jo;Tomita, Takehiro;Stevens, Kerrie;Schultz, Mark B;Baines, Sarah L;Sherry, Norelle L ;Carter, Glen P;Mu, Andre;Sait, Michelle;Ballard, Susan A;Seemann, Torsten;Stinear, Timothy P;Howden, Benjamin P 
Affiliation: Doherty Applied Microbial Genomics, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Health Protection Branch, Department of Health and Human Services, Victoria State Government, Melbourne, Victoria, Australia
Department of Microbiology, St Vincent's Hospital Melbourne, Fitzroy, Victoria, Australia
Melbourne Bioinformatics, The University of Melbourne, Carlton, Victoria, Australia
Issue Date: 2018 2018-01-03
Publication information: PeerJ 2018; 6: e4210
Abstract: Until recently,Klebsiella pneumoniaecarbapenemase (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. 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. Initial investigations indicated that the outbreak was widespread, with 86 KPC-producing Enterobacteriaceae isolates (K. pneumoniae92%) 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 inter-species 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. 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 real-time and the development of state-wide public health guidelines on carbapenemase-producing Enterobacteriaceae surveillance and management.
DOI: 10.7717/peerj.4210
ORCID: 0000-0002-0557-0518
Journal: PeerJ
PubMed URL: 29312831
ISSN: 2167-8359
Type: Journal Article
Subjects: Antimicrobial resistance
Klebsiella pneumoniae carbapenemase
Microbial genomics
Multidrug-resistant organisms
Outbreak investigation
Transmission modelling
Whole-genome sequencing
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