A high-resolution genomic analysis of multidrug-resistant hospital outbreaks of Klebsiella pneumoniae

被引：90

作者：

Hao Chung The ^{[1
]}

Karkey, Abhilasha ^{[2
]}

Duy Pham Thanh ^{[1
]}

Boinett, Christine J. ^{[3
]}

Cain, Amy K. ^{[3
]}

Ellington, Matthew ^{[3
,4
]}

Baker, Kate S. ^{[3
]}

Dongol, Sabina ^{[2
]}

Thompson, Corinne ^{[1
,5
]}

Harris, Simon R. ^{[3
]}

Jombart, Thibaut ^{[6
]}

Tu Le Thi Phuong ^{[1
]}

Nhu Tran Do Hoang ^{[1
]}

Tuyen Ha Thanh ^{[1
]}

Shretha, Shrijana ^{[2
]}

Joshi, Suchita ^{[2
]}

Basnyat, Buddha ^{[2
]}

Thwaites, Guy ^{[1
,5
]}

Thomson, Nicholas R. ^{[3
,7
]}

Rabaa, Maia A. ^{[1
,8
]}

Baker, Stephen ^{[1
,5
,7
]}

机构：

[1] Univ Oxford, Hosp Trop Dis, Wellcome Trust Major Overseas Programme, Clin Res Unit, Ho Chi Minh City, Vietnam

[2] Univ Oxford, Patan Acad Hlth Sci, Wellcome Trust Major Overseas Programme, Clin Res Unit, Kathmandu, Nepal

[3] Wellcome Trust Sanger Inst, Cambridge, England

[4] Addenbrookes Hosp, Cambridge, England

[5] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England

[6] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, Dept Infect Dis Epidemiol, Sch Publ Hlth, London, England

[7] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England

[8] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland

来源：

EMBO MOLECULAR MEDICINE | 2015年 / 7卷 / 03期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

antimicrobial resistance; bloodstream infections; carbapenemases; Klebsiella pneumoniae; nosocomial infections; SEQUENCE ALIGNMENT; IDENTIFICATION; ENTEROBACTERIACEAE; YERSINIABACTIN; CARBAPENEMASES; DISSEMINATION; EPIDEMIOLOGY; BLA(NDM-1); ALGORITHMS; EMERGENCE;

D O I：

10.15252/emmm.201404767

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite itsprominence, 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 6months 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.

引用

页码：227 / 239

页数：13

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