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First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal

Bibliographic Details
Main Author: Mendes, Gabriel
Publication Date: 2022
Other Authors: Ramalho, João Francisco, Bruschy-Fonseca, Ana, Lito, Luís, Duarte, Aida, Cristino, José Melo, Caneiras, Catia
Format: Article
Language: eng
Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Download full: http://hdl.handle.net/10451/51071
Summary: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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spelling First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from PortugalKPC-70Klebsiella pneumoniaeCeftazidime/Avibactam resistanceKPC-3ST13KPC-variantHypermucoviscosityHypervirulencePortugal© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).The combination of ceftazidime/avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales. Emerging cases caused by CZA-resistant strains that produce variants of KPC genes have already been reported worldwide. However, to the best of our knowledge, no CZA-resistant strains were reported in Portugal. In September 2019, a K. pneumoniae CZA-resistant strain was collected from ascitic fluid at a surgery ward of a tertiary University Hospital Center in Lisboa, Portugal. The strain was resistant to ceftazidime/avibactam, as well as to ceftazidime, cefoxitin, gentamicin, amoxicillin/clavulanic acid, and ertapenem, being susceptible to imipenem and tigecycline. A hypermucoviscosity phenotype was confirmed by string test. Whole-genome sequencing (WGS) analysis revealed the presence of an ST13 KPC70-producing K. pneumoniae, a KPC-3 variant, differing in two amino-acid substitutions (D179Y and T263A). The D179Y mutation in the KPC Ω-loop region is the most common amino-acid substitution in KPC-2 and KPC-3, further leading to CZA resistance. The second mutation causes a KPC-70 variant in which threonine replaces alanine (T263A). The CZA-resistant strain showed the capsular locus KL3 and antigen locus O1v2. Other important virulence factors were identified: fimbrial adhesins type 1 and type 3, as well as the cluster of iron uptake systems aerobactin, enterobactin, salmochelin, and yersiniabactin included in integrative conjugative element 10 (ICEKp10) with the genotoxin colibactin cluster. Herein, we report the molecular characterization of the first hypervirulent CZA-resistant ST13 KPC-70-producing K. pneumoniae strain in Portugal. The emergence of CZA-resistant strains might pose a serious threat to public health and suggests an urgent need for enhanced clinical awareness and epidemiologic surveillance.This research was partially funded by the Fundação para a Ciência e a Tecnologia (FCT), grant number UIDB/04295/2020 and UIDP/04295/2020. Gabriel Mendes (G.M.) is supported by the Fundação para a Ciência e Tecnologia (FCT), Portugal, through a PhD Research Studentship Contract (Contrato de Bolsa de Investigação para Doutoramento 2020.07736.BD). Cátia Caneiras (C.C.) acknowledges the funding provided by the “Research Award in Healthcare Associated Infections” granted by the Escola Superior de Saúde Norte da Cruz Vermelha Portuguesa (2019) and by the “BInov award”, an innovation award granted by Southern Regional and Autonomous Regions Section of the Portuguese Pharmaceutical Society (2021).MDPIRepositório da Universidade de LisboaMendes, GabrielRamalho, João FranciscoBruschy-Fonseca, AnaLito, LuísDuarte, AidaCristino, José MeloCaneiras, Catia2022-02-01T15:33:02Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51071engAntibiotics 2022, 11, 16710.3390/antibiotics110201672079-6382info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:40:47Zoai:repositorio.ulisboa.pt:10451/51071Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:21:28.298879Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal
title First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal
spellingShingle First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal
Mendes, Gabriel
KPC-70
Klebsiella pneumoniae
Ceftazidime/Avibactam resistance
KPC-3
ST13
KPC-variant
Hypermucoviscosity
Hypervirulence
Portugal
title_short First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal
title_full First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal
title_fullStr First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal
title_full_unstemmed First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal
title_sort First description of Ceftazidime/Avibactam resistance in an ST13 KPC-70-producing Klebsiella pneumoniae strain from Portugal
author Mendes, Gabriel
author_facet Mendes, Gabriel
Ramalho, João Francisco
Bruschy-Fonseca, Ana
Lito, Luís
Duarte, Aida
Cristino, José Melo
Caneiras, Catia
author_role author
author2 Ramalho, João Francisco
Bruschy-Fonseca, Ana
Lito, Luís
Duarte, Aida
Cristino, José Melo
Caneiras, Catia
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Mendes, Gabriel
Ramalho, João Francisco
Bruschy-Fonseca, Ana
Lito, Luís
Duarte, Aida
Cristino, José Melo
Caneiras, Catia
dc.subject.por.fl_str_mv KPC-70
Klebsiella pneumoniae
Ceftazidime/Avibactam resistance
KPC-3
ST13
KPC-variant
Hypermucoviscosity
Hypervirulence
Portugal
topic KPC-70
Klebsiella pneumoniae
Ceftazidime/Avibactam resistance
KPC-3
ST13
KPC-variant
Hypermucoviscosity
Hypervirulence
Portugal
description © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
publishDate 2022
dc.date.none.fl_str_mv 2022-02-01T15:33:02Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/51071
url http://hdl.handle.net/10451/51071
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Antibiotics 2022, 11, 167
10.3390/antibiotics11020167
2079-6382
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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