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...
- 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
- 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 |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.local.none.fl_str_mv |
Artículo de revista |
dc.type.coar.none.fl_str_mv |
http://purl.org/coar/resource_type/c_6501 |
dc.type.driver.none.fl_str_mv |
info:eu-repo/semantics/article |
format |
http://purl.org/coar/resource_type/c_6501 |
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 |
dc.identifier.repourl.none.fl_str_mv |
repourl:https://repositorio.unbosque.edu.co |
identifier_str_mv |
2328-8957 instname:Universidad El Bosque reponame:Repositorio Institucional Universidad El Bosque repourl:https://repositorio.unbosque.edu.co |
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 |
dc.rights.uri.*.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.rights.local.spa.fl_str_mv |
Acceso abierto |
dc.rights.accessrights.none.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess Acceso abierto |
dc.rights.creativecommons.none.fl_str_mv |
2019-07 |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ Acceso abierto http://purl.org/coar/access_right/c_abf2 2019-07 |
eu_rights_str_mv |
openAccess |
dc.format.mimetype.none.fl_str_mv |
application/pdf |
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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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. Phylogenetic analysis suggests that ST309 P aeruginosa may be an emerging threat in the United States.ORIGINALKhan_Ayesha_2019.pdfKhan_Ayesha_2019.pdfapplication/pdf671655https://repositorio.unbosque.edu.co/bitstreams/45a9645b-99eb-4248-8fd0-b4c517fee925/download908da8194ed581819c27e22b03753e6dMD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805https://repositorio.unbosque.edu.co/bitstreams/ae1bd080-82cf-439f-9be4-1a19eba7d580/download4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://repositorio.unbosque.edu.co/bitstreams/3f3ca70f-9748-4efe-b5ce-c4b3d85ed5ee/download8a4605be74aa9ea9d79846c1fba20a33MD53THUMBNAILKhan_Ayesha_2019.pdf.jpgKhan_Ayesha_2019.pdf.jpgIM Thumbnailimage/jpeg14097https://repositorio.unbosque.edu.co/bitstreams/24789d60-fad4-4ac5-afc4-0149d17e10b9/download419f005e4270b34512af386286020d9cMD54TEXTKhan_Ayesha_2019.pdf.txtKhan_Ayesha_2019.pdf.txtExtracted texttext/plain41234https://repositorio.unbosque.edu.co/bitstreams/fcb430a7-2326-4162-ba00-e784b1f3f1b0/download9c70f0b13eb62a9d978fce83a1368b53MD5520.500.12495/5245oai:repositorio.unbosque.edu.co:20.500.12495/52452024-02-06 23:55:55.257http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accesshttps://repositorio.unbosque.edu.coRepositorio Institucional Universidad El Bosquebibliotecas@biteca.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 |