Plasmid Dynamics in KPC-Positive <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> during Long-Term Patient Colonization

ABSTRACT Carbapenem-resistant Klebsiella pneumoniae strains are formidable hospital pathogens that pose a serious threat to patients around the globe due to a rising incidence in health care facilities, high mortality rates associated with infection, and potential to spread antibiotic resistance to...

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Autores principales: Sean Conlan, Morgan Park, Clayton Deming, Pamela J. Thomas, Alice C. Young, Holly Coleman, Christina Sison, Rebecca A. Weingarten, Anna F. Lau, John P. Dekker, Tara N. Palmore, Karen M. Frank, Julia A. Segre
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Publicado: American Society for Microbiology 2016
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spelling oai:doaj.org-article:9a8bf545fee74e25a9ca4f743bea2d402021-11-15T15:50:17ZPlasmid Dynamics in KPC-Positive <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> during Long-Term Patient Colonization10.1128/mBio.00742-162150-7511https://doaj.org/article/9a8bf545fee74e25a9ca4f743bea2d402016-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00742-16https://doaj.org/toc/2150-7511ABSTRACT Carbapenem-resistant Klebsiella pneumoniae strains are formidable hospital pathogens that pose a serious threat to patients around the globe due to a rising incidence in health care facilities, high mortality rates associated with infection, and potential to spread antibiotic resistance to other bacterial species, such as Escherichia coli. Over 6 months in 2011, 17 patients at the National Institutes of Health (NIH) Clinical Center became colonized with a highly virulent, transmissible carbapenem-resistant strain of K. pneumoniae. Our real-time genomic sequencing tracked patient-to-patient routes of transmission and informed epidemiologists’ actions to monitor and control this outbreak. Two of these patients remained colonized with carbapenemase-producing organisms for at least 2 to 4 years, providing the opportunity to undertake a focused genomic study of long-term colonization with antibiotic-resistant bacteria. Whole-genome sequencing studies shed light on the underlying complex microbial colonization, including mixed or evolving bacterial populations and gain or loss of plasmids. Isolates from NIH patient 15 showed complex plasmid rearrangements, leaving the chromosome and the blaKPC-carrying plasmid intact but rearranging the two other plasmids of this outbreak strain. NIH patient 16 has shown continuous colonization with blaKPC-positive organisms across multiple time points spanning 2011 to 2015. Genomic studies defined a complex pattern of succession and plasmid transmission across two different K. pneumoniae sequence types and an E. coli isolate. These findings demonstrate the utility of genomic methods for understanding strain succession, genome plasticity, and long-term carriage of antibiotic-resistant organisms. IMPORTANCE In 2011, the NIH Clinical Center had a nosocomial outbreak involving 19 patients who became colonized or infected with blaKPC-positive Klebsiella pneumoniae. Patients who have intestinal colonization with blaKPC-positive K. pneumoniae are at risk for developing infections that are difficult or nearly impossible to treat with existing antibiotic options. Two of those patients remained colonized with blaKPC-positive Klebsiella pneumoniae for over a year, leading to the initiation of a detailed genomic analysis exploring mixed colonization, plasmid recombination, and plasmid diversification. Whole-genome sequence analysis identified a variety of changes, both subtle and large, in the blaKPC-positive organisms. Long-term colonization of patients with blaKPC-positive Klebsiella pneumoniae creates new opportunities for horizontal gene transfer of plasmids encoding antibiotic resistance genes and poses complications for the delivery of health care.Sean ConlanMorgan ParkClayton DemingPamela J. ThomasAlice C. YoungHolly ColemanChristina SisonRebecca A. WeingartenAnna F. LauJohn P. DekkerTara N. PalmoreKaren M. FrankJulia A. SegreAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 3 (2016)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Sean Conlan
Morgan Park
Clayton Deming
Pamela J. Thomas
Alice C. Young
Holly Coleman
Christina Sison
Rebecca A. Weingarten
Anna F. Lau
John P. Dekker
Tara N. Palmore
Karen M. Frank
Julia A. Segre
Plasmid Dynamics in KPC-Positive <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> during Long-Term Patient Colonization
description ABSTRACT Carbapenem-resistant Klebsiella pneumoniae strains are formidable hospital pathogens that pose a serious threat to patients around the globe due to a rising incidence in health care facilities, high mortality rates associated with infection, and potential to spread antibiotic resistance to other bacterial species, such as Escherichia coli. Over 6 months in 2011, 17 patients at the National Institutes of Health (NIH) Clinical Center became colonized with a highly virulent, transmissible carbapenem-resistant strain of K. pneumoniae. Our real-time genomic sequencing tracked patient-to-patient routes of transmission and informed epidemiologists’ actions to monitor and control this outbreak. Two of these patients remained colonized with carbapenemase-producing organisms for at least 2 to 4 years, providing the opportunity to undertake a focused genomic study of long-term colonization with antibiotic-resistant bacteria. Whole-genome sequencing studies shed light on the underlying complex microbial colonization, including mixed or evolving bacterial populations and gain or loss of plasmids. Isolates from NIH patient 15 showed complex plasmid rearrangements, leaving the chromosome and the blaKPC-carrying plasmid intact but rearranging the two other plasmids of this outbreak strain. NIH patient 16 has shown continuous colonization with blaKPC-positive organisms across multiple time points spanning 2011 to 2015. Genomic studies defined a complex pattern of succession and plasmid transmission across two different K. pneumoniae sequence types and an E. coli isolate. These findings demonstrate the utility of genomic methods for understanding strain succession, genome plasticity, and long-term carriage of antibiotic-resistant organisms. IMPORTANCE In 2011, the NIH Clinical Center had a nosocomial outbreak involving 19 patients who became colonized or infected with blaKPC-positive Klebsiella pneumoniae. Patients who have intestinal colonization with blaKPC-positive K. pneumoniae are at risk for developing infections that are difficult or nearly impossible to treat with existing antibiotic options. Two of those patients remained colonized with blaKPC-positive Klebsiella pneumoniae for over a year, leading to the initiation of a detailed genomic analysis exploring mixed colonization, plasmid recombination, and plasmid diversification. Whole-genome sequence analysis identified a variety of changes, both subtle and large, in the blaKPC-positive organisms. Long-term colonization of patients with blaKPC-positive Klebsiella pneumoniae creates new opportunities for horizontal gene transfer of plasmids encoding antibiotic resistance genes and poses complications for the delivery of health care.
format article
author Sean Conlan
Morgan Park
Clayton Deming
Pamela J. Thomas
Alice C. Young
Holly Coleman
Christina Sison
Rebecca A. Weingarten
Anna F. Lau
John P. Dekker
Tara N. Palmore
Karen M. Frank
Julia A. Segre
author_facet Sean Conlan
Morgan Park
Clayton Deming
Pamela J. Thomas
Alice C. Young
Holly Coleman
Christina Sison
Rebecca A. Weingarten
Anna F. Lau
John P. Dekker
Tara N. Palmore
Karen M. Frank
Julia A. Segre
author_sort Sean Conlan
title Plasmid Dynamics in KPC-Positive <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> during Long-Term Patient Colonization
title_short Plasmid Dynamics in KPC-Positive <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> during Long-Term Patient Colonization
title_full Plasmid Dynamics in KPC-Positive <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> during Long-Term Patient Colonization
title_fullStr Plasmid Dynamics in KPC-Positive <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> during Long-Term Patient Colonization
title_full_unstemmed Plasmid Dynamics in KPC-Positive <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> during Long-Term Patient Colonization
title_sort plasmid dynamics in kpc-positive <named-content content-type="genus-species">klebsiella pneumoniae</named-content> during long-term patient colonization
publisher American Society for Microbiology
publishDate 2016
url https://doaj.org/article/9a8bf545fee74e25a9ca4f743bea2d40
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