Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states

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dc.contributor.authorTran, Truc T.
dc.contributor.authorRios, Rafael
dc.contributor.authorHanson, Blake
dc.contributor.authorShropshire, William C.
dc.contributor.authorSun, Zhizeng
dc.contributor.authorDiaz, Lorena
dc.contributor.authorDinh, An Q.
dc.contributor.authorWanger, Audrey
dc.contributor.authorOstrosky-Zeichner, Luis
dc.contributor.authorPalzkill, Timothy
dc.contributor.authorArias, Cesar A.
dc.contributor.authorMiller, William R.
dc.date.accessioned2021-02-04T19:48:24Z
dc.date.available2021-02-04T19:48:24Z
dc.date.issued2019
dc.description.abstractenglishTreatment of serious infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa remains a challenge, despite the introduction of novel therapeutics. In this study, we report 2 extensively drug-resistant clinical isolates of sequence type (ST) 309 P aeruginosa resistant to all β-lactams, including the novel combinations ceftolozane/tazobactam, ceftazidime/avibactam, and meropenem/vaborbactam. Isolates were sequenced using both short-read (Illumina) and long-read technology to identify resistance determinants, polymorphisms (compared with P aeruginosa PAO1), and reconstruct a phylogenetic tree. A pair of β-lactamases, Guiana extended spectrum β-lactamase (GES)-19 and GES-26, were cloned and expressed in a laboratory strain of Escherichia coli to examine their relative impact on resistance. Using cell lysates from E coli expressing the GES genes individually and in tandem, we determined relative rates of hydrolysis for nitrocefin and ceftazidime. Two ST309 P aeruginosa clinical isolates were found to harbor the extended spectrum β-lactamases GES-19 and GES-26 clustered in tandem on a chromosomal class 1 integron. The presence of both enzymes in E coli was associated with significantly elevated minimum inhibitory concentrations to aztreonam, cefepime, meropenem, ceftazidime/avibactam, and ceftolozane/tazobactam, compared with those expressed individually. The combination of ceftazidime/avibactam plus aztreonam was active in vitro and used to achieve cure in one patient. Phylogenetic analysis revealed ST309 P aeruginosa are closely related to MDR strains from Mexico also carrying tandem GES. The presence of tandem GES-19 and GES-26 is associated with resistance to all β-lactams, including ceftolozane/tazobactam. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1093/ofid/ofz273
dc.identifier.instnameinstname:Universidad El Bosquespa
dc.identifier.issn2328-8957
dc.identifier.reponamereponame:Repositorio Institucional Universidad El Bosquespa
dc.identifier.repourlrepourl:https://repositorio.unbosque.edu.co
dc.identifier.urihttps://hdl.handle.net/20.500.12495/5245
dc.language.isoeng
dc.publisherOxford University Pressspa
dc.publisher.journalOpen Forum Infectious Diseasesspa
dc.relation.ispartofseriesOpen Forum Infectious Diseases, 2328-8957, Vol. 6, No. 7, 2019, p. 1-7spa
dc.relation.urihttps://academic.oup.com/ofid/article/6/7/ofz273/5512661
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.accessrightshttps://purl.org/coar/access_right/c_abf2
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess
dc.rights.accessrightsAcceso abierto
dc.rights.creativecommons2019-07
dc.rights.localAcceso abiertospa
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.keywordsGES beta-lactamasespa
dc.subject.keywordsCarbapenem-resistant Pseudomonas aeruginosaspa
dc.subject.keywordsCeftolozane/tazobactamspa
dc.subject.keywordsCombination therapyspa
dc.titleExtensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united statesspa
dc.title.translatedExtensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united statesspa
dc.type.coarhttps://purl.org/coar/resource_type/c_6501
dc.type.driverinfo:eu-repo/semantics/article
dc.type.hasversioninfo:eu-repo/semantics/publishedVersion
dc.type.localArtículo de revista

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