{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:46:01Z","timestamp":1790959561911,"version":"4.1.0"},"reference-count":28,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2016,6,28]],"date-time":"2016-06-28T00:00:00Z","timestamp":1467072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000272","name":"DH | National Institute for Health Research","doi-asserted-by":"publisher","award":["1ZIAHG200382-04"],"award-info":[{"award-number":["1ZIAHG200382-04"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000098","name":"HHS | NIH | NIH Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2016,7,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Carbapenem-resistant\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            . Over 6\u00a0months in 2011, 17 patients at the National Institutes of Health (NIH) Clinical Center became colonized with a highly virulent, transmissible carbapenem-resistant strain of\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            . Our real-time genomic sequencing tracked patient-to-patient routes of transmission and informed epidemiologists\u2019 actions to monitor and control this outbreak. Two of these patients remained colonized with carbapenemase-producing organisms for at least 2 to 4\u00a0years, 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\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            -carrying plasmid intact but rearranging the two other plasmids of this outbreak strain. NIH patient 16 has shown continuous colonization with\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            -positive organisms across multiple time points spanning 2011 to 2015. Genomic studies defined a complex pattern of succession and plasmid transmission across two different\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            sequence types and an\n            <jats:named-content content-type=\"genus-species\">E. coli<\/jats:named-content>\n            isolate. These findings demonstrate the utility of genomic methods for understanding strain succession, genome plasticity, and long-term carriage of antibiotic-resistant organisms.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            In 2011, the NIH Clinical Center had a nosocomial outbreak involving 19 patients who became colonized or infected with\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            -positive\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            . Patients who have intestinal colonization with\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            -positive\n            <jats:named-content content-type=\"genus-species\">K. pneumoniae<\/jats:named-content>\n            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\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            -positive\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            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\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            -positive organisms. Long-term colonization of patients with\n            <jats:italic>bla<\/jats:italic>\n            <jats:sub>KPC<\/jats:sub>\n            -positive\n            <jats:named-content content-type=\"genus-species\">Klebsiella pneumoniae<\/jats:named-content>\n            creates new opportunities for horizontal gene transfer of plasmids encoding antibiotic resistance genes and poses complications for the delivery of health care.\n          <\/jats:p>","DOI":"10.1128\/mbio.00742-16","type":"journal-article","created":{"date-parts":[[2016,6,29]],"date-time":"2016-06-29T18:20:21Z","timestamp":1467224421000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":110,"title":["Plasmid Dynamics in KPC-Positive Klebsiella pneumoniae during Long-Term Patient Colonization"],"prefix":"10.1128","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6848-3465","authenticated-orcid":false,"given":"Sean","family":"Conlan","sequence":"first","affiliation":[{"name":"National Human Genome Research Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Park","sequence":"additional","affiliation":[{"name":"National Institutes of Health Intramural Sequencing Center (NISC), Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clayton","family":"Deming","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela J.","family":"Thomas","sequence":"additional","affiliation":[{"name":"National Institutes of Health Intramural Sequencing Center (NISC), Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice C.","family":"Young","sequence":"additional","affiliation":[{"name":"National Institutes of Health Intramural Sequencing Center (NISC), Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Coleman","sequence":"additional","affiliation":[{"name":"National Institutes of Health Intramural Sequencing Center (NISC), Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Sison","sequence":"additional","affiliation":[{"name":"National Institutes of Health Intramural Sequencing Center (NISC), Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"NISC Comparative Sequencing Program","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca A.","family":"Weingarten","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna F.","family":"Lau","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Dekker","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara N.","family":"Palmore","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen M.","family":"Frank","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia A.","family":"Segre","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Annual Report of the Chief Medical Officer, England","author":"Davies SC","year":"2011","unstructured":"Davies SC. 2011. Infections and the rise of antimicrobial resistance, vol 2. Annual Report of the Chief Medical Officer, England. United Kingdom Department of Health, London, England."},{"key":"e_1_3_2_3_2","unstructured":"President\u2019s Council of Advisors on Science and Technology. 2014. Report to the President on combating antibiotic resistance. Executive Office of the President. https:\/\/www.whitehouse.gov\/sites\/default\/files\/microsites\/ostp\/PCAST\/pcast_carb_report_sept2014.pdf."},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2012.03.003"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2015.04.002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3009845"},{"key":"e_1_3_2_7_2","volume-title":"Vital signs telebriefing on carbapenem-resistant Enterobacteriaceae","author":"Frieden T","year":"2013","unstructured":"Frieden T. 2013. 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