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

PeerJ

article

Jason C. Kwong¹  Courtney R. Lane⁴  Finn Romanes⁵  Anders Gonçalves da Silva¹  Marion Easton⁵  Katie Cronin⁶  Mary Jo Waters⁶  Takehiro Tomita⁴  Kerrie Stevens⁴  Mark B. Schultz¹  Sarah L. Baines¹  Norelle L. Sherry¹  Glen P. Carter¹  Andre Mu¹  Michelle Sait⁴  Susan A. Ballard¹  Torsten Seemann¹  Timothy P. Stinear¹  Benjamin P. Howden¹ 

[1] Doherty Applied Microbial Genomics, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity;Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity;Department of Infectious Diseases, Austin Health;Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity;Health Protection Branch, Department of Health and Human Services;Department of Microbiology, St Vincent’s Hospital Melbourne;Melbourne Bioinformatics, The University of Melbourne

关键词: Klebsiella pneumoniae carbapenemase;    Outbreak investigation;    Whole-genome sequencing;    Microbial genomics;    Transmission modelling;    Antimicrobial resistance;    Multidrug-resistant organisms;   

DOI  :  10.7717/peerj.4210

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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 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. 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 real-time and the development of state-wide public health guidelines on carbapenemase-producing Enterobacteriaceae surveillance and management.

【 授权许可】

CC BY