title: A high-resolution genomic analysis of multidrug-resistant hospital outbreaks of Klebsiella pneumoniae.
abstract: Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource-poor hospital settings. Through whole-genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high-dependency wards in a hospital in Kathmandu during 2012 with a case-fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae. Using phylogenetic reconstruction and lineage-specific PCR, our data predicted a scenario in which K. pneumoniae, circulating for 6 months before the outbreak, underwent a series of ward-specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM-1 containing lineage in 2011 would have alerted the high-dependency ward staff to intervene. We argue that some form of real-time genetic characterisation, alongside clade-specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high- and low-income settings.
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Hao
authors.initials: H
authors.lastname: Chung The
authors.affiliation: Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
authors.forename: Abhilasha
authors.initials: A
authors.lastname: Karkey
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Duy
authors.initials: D
authors.lastname: Pham Thanh
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Boinett
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Cain
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ellington
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK.
authors.forename: Kate S
authors.initials: KS
authors.lastname: Baker
authors.affiliation: Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
authors.forename: Sabina
authors.initials: S
authors.lastname: Dongol
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
authors.forename: Corinne
authors.initials: C
authors.lastname: Thompson
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK.
authors.forename: Simon R
authors.initials: SR
authors.lastname: Harris
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, School of Public Health, Imperial College, London, UK.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Jombart
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Tu
authors.initials: T
authors.lastname: Le Thi Phuong
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Nhu
authors.initials: N
authors.lastname: Tran Do Hoang
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Tuyen
authors.initials: T
authors.lastname: Ha Thanh
authors.affiliation: Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
authors.forename: Shrijana
authors.initials: S
authors.lastname: Shretha
authors.affiliation: Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
authors.forename: Suchita
authors.initials: S
authors.lastname: Joshi
authors.affiliation: Patan Academy of Health Sciences, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Kathmandu, Nepal.
authors.forename: Buddha
authors.initials: B
authors.lastname: Basnyat
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.
authors.forename: Guy
authors.initials: G
authors.lastname: Thwaites
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton Cambridge, UK The London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Immunity, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Maia A
authors.initials: MA
authors.lastname: Rabaa
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK The London School of Hygiene and Tropical Medicine, London, UK sbaker@oucru.org.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D023281:Genomics; D005838:Genotype; D006801:Humans; D017053:Infection Control / Q000379:methods; D007710:Klebsiella Infections / Q000453:epidemiology* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000145:classification* / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D008969:Molecular Sequence Data; D009390:Nepal / Q000453:epidemiology; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D037521:Virulence Factors / Q000235:genetics
chemical_list: D037521:Virulence Factors
keywords: Klebsiella pneumoniae; antimicrobial resistance; bloodstream infections; carbapenemases; nosocomial infections