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Research Article | Clinical Science and Epidemiology

Molecular Epidemiology of Colonizing and Infecting Isolates of Klebsiella pneumoniae

Rebekah M. Martin, Jie Cao, Sylvain Brisse, Virginie Passet, Weisheng Wu, Lili Zhao, Preeti N. Malani, Krishna Rao, Michael A. Bachman
Mariana Castanheira, Editor
Rebekah M. Martin
aDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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Jie Cao
aDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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Sylvain Brisse
bInstitut Pasteur, Microbial Evolutionary Genomics, Paris, France
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Virginie Passet
bInstitut Pasteur, Microbial Evolutionary Genomics, Paris, France
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Weisheng Wu
cBRCF Bioinformatics Core, University of Michigan, Ann Arbor, Michigan, USA
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Lili Zhao
dDepartment of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA
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Preeti N. Malani
eDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
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Krishna Rao
eDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA
fSection of Infectious Diseases, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, USA
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Michael A. Bachman
aDepartment of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA
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Mariana Castanheira
JMI Laboratories
Roles: Editor
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DOI: 10.1128/mSphere.00261-16
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ABSTRACT

Klebsiella pneumoniae is among the most common causes of hospital-acquired infections and has emerged as an urgent threat to public health due to carbapenem antimicrobial resistance. K. pneumoniae commonly colonizes hospitalized patients and causes extraintestinal infections such as urinary tract infection, bloodstream infection (septicemia), and pneumonia. If colonization is an intermediate step before infection, then detection and characterization of colonizing isolates could enable strategies to prevent or empirically treat K. pneumoniae infections in hospitalized patients. However, the strength of the association between colonization and infection is unclear. To test the hypothesis that hospitalized patients become infected with their colonizing strain, 1,765 patients were screened for rectal colonization with K. pneumoniae, and extraintestinal isolates from these same patients were collected over a 3-month period in a cohort study design. The overall colonization prevalence was 23.0%. After adjustment for other patient factors, colonization was significantly associated with subsequent infection: 21 of 406 (5.2%) colonized patients later had extraintestinal infection, compared to 18 of 1,359 (1.3%) noncolonized patients (adjusted odds ratio [OR], 4.01; 95% confidence interval, 2.08 to 7.73; P < 0.001). Despite a high diversity of colonizing isolates, 7/7 respiratory, 4/4 urinary, and 2/5 bloodstream isolates from colonized patients matched the patient corresponding rectal swab isolates, based on wzi capsular typing, multilocus sequence typing (MLST), and whole-genome sequence analysis. These results suggest that K. pneumoniae colonization is directly associated with progression to extraintestinal infection.

IMPORTANCE K. pneumoniae commonly infects hospitalized patients, and these infections are increasingly resistant to carbapenems, the antibiotics of last resort for life-threatening bacterial infections. To prevent and treat these infections, we must better understand how K. pneumoniae causes disease and discover new ways to predict and detect infections. This study demonstrates that colonization with K. pneumoniae in the intestinal tract is strongly linked to subsequent infection. This finding helps to identify a potential time frame and possible approach for intervention: the colonizing strain from a patient could be isolated as part of a risk assessment, and antibiotic susceptibility testing could guide empirical therapy if the patient becomes acutely ill.

  • Copyright © 2016 Martin et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license .

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Molecular Epidemiology of Colonizing and Infecting Isolates of Klebsiella pneumoniae
Rebekah M. Martin, Jie Cao, Sylvain Brisse, Virginie Passet, Weisheng Wu, Lili Zhao, Preeti N. Malani, Krishna Rao, Michael A. Bachman
mSphere Oct 2016, 1 (5) e00261-16; DOI: 10.1128/mSphere.00261-16

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Molecular Epidemiology of Colonizing and Infecting Isolates of Klebsiella pneumoniae
Rebekah M. Martin, Jie Cao, Sylvain Brisse, Virginie Passet, Weisheng Wu, Lili Zhao, Preeti N. Malani, Krishna Rao, Michael A. Bachman
mSphere Oct 2016, 1 (5) e00261-16; DOI: 10.1128/mSphere.00261-16
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KEYWORDS

Klebsiella
MLST
cgMLST
colonization
infection
pneumonia
whole-genome sequencing
wzi

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