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

Treatment 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, incl...

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Autores:
Tran, Truc T.
Rios, Rafael
Hanson, Blake
Shropshire, William C.
Sun, Zhizeng
Diaz, Lorena
Dinh, An Q.
Wanger, Audrey
Ostrosky-Zeichner, Luis
Palzkill, Timothy
Arias, Cesar A.
Miller, William R.
Tipo de recurso:
Article of journal
Fecha de publicación:
2019
Institución:
Universidad El Bosque
Repositorio:
Repositorio U. El Bosque
Idioma:
eng
OAI Identifier:
oai:repositorio.unbosque.edu.co:20.500.12495/5245
Acceso en línea:
http://hdl.handle.net/20.500.12495/5245
https://doi.org/10.1093/ofid/ofz273
Palabra clave:
GES beta-lactamase
Carbapenem-resistant Pseudomonas aeruginosa
Ceftolozane/tazobactam
Combination therapy
Rights
openAccess
License
Attribution-NonCommercial-NoDerivatives 4.0 International
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dc.title.spa.fl_str_mv Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
dc.title.translated.spa.fl_str_mv Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
title Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
spellingShingle Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
GES beta-lactamase
Carbapenem-resistant Pseudomonas aeruginosa
Ceftolozane/tazobactam
Combination therapy
title_short Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
title_full Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
title_fullStr Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
title_full_unstemmed Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
title_sort Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united states
dc.creator.fl_str_mv Tran, Truc T.
Rios, Rafael
Hanson, Blake
Shropshire, William C.
Sun, Zhizeng
Diaz, Lorena
Dinh, An Q.
Wanger, Audrey
Ostrosky-Zeichner, Luis
Palzkill, Timothy
Arias, Cesar A.
Miller, William R.
dc.contributor.author.none.fl_str_mv Tran, Truc T.
Rios, Rafael
Hanson, Blake
Shropshire, William C.
Sun, Zhizeng
Diaz, Lorena
Dinh, An Q.
Wanger, Audrey
Ostrosky-Zeichner, Luis
Palzkill, Timothy
Arias, Cesar A.
Miller, William R.
dc.subject.keywords.spa.fl_str_mv GES beta-lactamase
Carbapenem-resistant Pseudomonas aeruginosa
Ceftolozane/tazobactam
Combination therapy
topic GES beta-lactamase
Carbapenem-resistant Pseudomonas aeruginosa
Ceftolozane/tazobactam
Combination therapy
description Treatment 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.
publishDate 2019
dc.date.issued.none.fl_str_mv 2019
dc.date.accessioned.none.fl_str_mv 2021-02-04T19:48:24Z
dc.date.available.none.fl_str_mv 2021-02-04T19:48:24Z
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dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.local.none.fl_str_mv Artículo de revista
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dc.identifier.issn.none.fl_str_mv 2328-8957
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/20.500.12495/5245
dc.identifier.doi.none.fl_str_mv https://doi.org/10.1093/ofid/ofz273
dc.identifier.instname.spa.fl_str_mv instname:Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad El Bosque
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identifier_str_mv 2328-8957
instname:Universidad El Bosque
reponame:Repositorio Institucional Universidad El Bosque
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url http://hdl.handle.net/20.500.12495/5245
https://doi.org/10.1093/ofid/ofz273
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.ispartofseries.spa.fl_str_mv Open Forum Infectious Diseases, 2328-8957, Vol. 6, No. 7, 2019, p. 1-7
dc.relation.uri.none.fl_str_mv https://academic.oup.com/ofid/article/6/7/ofz273/5512661
dc.rights.*.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
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dc.rights.local.spa.fl_str_mv Acceso abierto
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Acceso abierto
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rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 International
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eu_rights_str_mv openAccess
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dc.publisher.spa.fl_str_mv Oxford University Press
dc.publisher.journal.spa.fl_str_mv Open Forum Infectious Diseases
institution Universidad El Bosque
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spelling Tran, Truc T.Rios, RafaelHanson, BlakeShropshire, William C.Sun, ZhizengDiaz, LorenaDinh, An Q.Wanger, AudreyOstrosky-Zeichner, LuisPalzkill, TimothyArias, Cesar A.Miller, William R.2021-02-04T19:48:24Z2021-02-04T19:48:24Z20192328-8957http://hdl.handle.net/20.500.12495/5245https://doi.org/10.1093/ofid/ofz273instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquerepourl:https://repositorio.unbosque.edu.coapplication/pdfengOxford University PressOpen Forum Infectious DiseasesOpen Forum Infectious Diseases, 2328-8957, Vol. 6, No. 7, 2019, p. 1-7https://academic.oup.com/ofid/article/6/7/ofz273/5512661Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Acceso abiertohttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessAcceso abierto2019-07Extensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united statesExtensively drug-resistant pseudomonas aeruginosa ST309 harboring tandem Guiana extended spectrum β-lactamase enzymes: a newly emerging threat in the united statesArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1info:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85GES beta-lactamaseCarbapenem-resistant Pseudomonas aeruginosaCeftolozane/tazobactamCombination therapyTreatment 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. 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