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Six worrisome nosocomial pathogens\u2014\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterococcus faecium<\/jats:named-content>\n                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Klebsiella pneumoniae<\/jats:named-content>\n                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Acinetobacter baumannii<\/jats:named-content>\n                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n                    , and\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Enterobacter<\/jats:named-content>\n                    spp.\u2014are collectively referred to as the \u201cESKAPE bugs.\u201d They are notorious for extensive multidrug resistance, yet persistence, or the phenotypic tolerance displayed by a variant subpopulation, remains underappreciated in these pathogens. Importantly, persistence can prevent eradication of antibiotic-sensitive bacterial populations and is thought to act as a catalyst for the development of genetic resistance. Concentration- and time-dependent aminoglycoside killing experiments were used to investigate persistence in the ESKAPE pathogens. Additionally, a recently developed method for the experimental evolution of persistence was employed to investigate adaptation to high-dose, extended-interval aminoglycoside therapy\n                    <jats:italic>in vitro<\/jats:italic>\n                    . We show that ESKAPE pathogens exhibit biphasic killing kinetics, indicative of persister formation.\n                    <jats:italic>In vitro<\/jats:italic>\n                    cycling between aminoglycoside killing and persister cell regrowth, evocative of clinical high-dose extended-interval therapy, caused a 37- to 213-fold increase in persistence without the emergence of resistance. Increased persistence also manifested in biofilms and provided cross-tolerance to different clinically important antibiotics. Together, our results highlight a possible drawback of intermittent, high-dose antibiotic therapy and suggest that clinical diagnostics might benefit from taking into account persistence.\n                  <\/jats:p>","DOI":"10.1128\/aac.00757-16","type":"journal-article","created":{"date-parts":[[2016,5,16]],"date-time":"2016-05-16T22:39:50Z","timestamp":1463438390000},"page":"4630-4637","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":100,"title":["<i>In Vitro<\/i>\n                    Emergence of High Persistence upon Periodic Aminoglycoside Challenge in the ESKAPE Pathogens"],"prefix":"10.1128","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2169-3507","authenticated-orcid":false,"given":"Joran Elie","family":"Michiels","sequence":"first","affiliation":[{"name":"Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4429-9780","authenticated-orcid":false,"given":"Bram","family":"Van den Bergh","sequence":"additional","affiliation":[{"name":"Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Verstraeten","sequence":"additional","affiliation":[{"name":"Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten","family":"Fauvart","sequence":"additional","affiliation":[{"name":"Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium"},{"name":"Smart Systems and Emerging Technologies Unit, Department of Life Science Technologies, imec, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Michiels","sequence":"additional","affiliation":[{"name":"Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","volume-title":"Antimicrobial resistance: global report on surveillance","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. 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