Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon

Antimicrobial resistance is one of the greatest threats to public health. Carbapenems are among the few useful antibiotics against multidrug resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome of clinical carbapenem-resistant Enterobacteriaceae recovere...

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Main Author: El Khoury, Maria (author)
Format: masterThesis
Published: 2020
Subjects:
Online Access:http://hdl.handle.net/10725/13473
https://doi.org/10.26756/th.2022.313
http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php
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author El Khoury, Maria
author_facet El Khoury, Maria
author_role author
dc.creator.none.fl_str_mv El Khoury, Maria
dc.date.none.fl_str_mv 2020
2020-07-29
2022-04-11T12:13:39Z
2022-04-11T12:13:39Z
dc.identifier.none.fl_str_mv http://hdl.handle.net/10725/13473
https://doi.org/10.26756/th.2022.313
http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php
dc.language.none.fl_str_mv en
dc.publisher.none.fl_str_mv Lebanese American University
dc.rights.*.fl_str_mv info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Enterobacteriaceae -- Molecular aspects
Beta lactam antibiotics
Drug resistance in microorganisms
Enterobacteriaceae -- Lebanon
Lebanese American University -- Dissertations
Dissertations, Academic
dc.title.none.fl_str_mv Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon
dc.type.none.fl_str_mv Thesis
info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/masterThesis
description Antimicrobial resistance is one of the greatest threats to public health. Carbapenems are among the few useful antibiotics against multidrug resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome of clinical carbapenem-resistant Enterobacteriaceae recovered in the period between 2016-2019 from hospitalized patients in Lebanon. The studied population included: 27 Escherichia coli, 24 Klebsiella pneumoniae, one K. quasipneumoniae, three Morganella morganii, three Citrobacter freundii, five Enterobacter hormaechei, and two Serratia marcescens. Antimicrobial susceptibility testing using the disk diffusion assay, carbapenemase confirmatory testing, and in silico whole-genome based analysis revealed that the majority of the isolates (87.7%; n=57) were carbapenem resistant harboring a broad range of carbapenemases. blaOXA-48 (33.8%; n=22) and blaOXA-48-like genes were among the detected resistance determinants, with two isolates additionally co-harboring the blaNDM-5. All OXA-48 producing isolates were ESBL and/or AmpC producers and were additionally resistant to non-β-lactam antibiotics. Carbapenem resistance determinants related to blaNDM were also detected including blaNDM-1 (16.9%; n=11), blaNDM-5 (9.2%; n=6), blaNDM-7 (9.2%; n=6), and blaNDM-19 (4.6%; n=3). A wide variety of ESBLs (OXA, SHV, TEM, CTX-M) and AmpC β-lactamases (CMY, DHA, ACT) were among the detected resistance determinants and of which blaCTX-M-15 (58.5%; n=38) and blaOXA-1 (53.8%; n=35) were the most common. Our study revealed a wide variety of incompatibility groups to be associated with carbapenem resistance with the IncFIB(K) (43.1%; n=28) being the most prevalent, followed by IncFIA (40.0%), IncL (35.4%), IncX3 (32.3%), IncI1 (32.3%), IncFIIK (29.2%). It was also the largest genome-based study in the region, revealing the tremendous heterogeneity, plasmid content, and various resistance determinants circulating in the country. High-risk carbapenem-resistant Enterobacteriaceae clones pose a significant threat to patients and healthcare systems in Lebanon. The observed plethora of plasmid-encoded resistance genes shed light on implementing corrective measures to mitigate the spread of carbapenem resistance.
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id LAURepo_2c9c4951dfdeed32172004374230ae96
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network_acronym_str LAURepo
network_name_str Lebanese American University repository
oai_identifier_str oai:laur.lau.edu.lb:10725/13473
publishDate 2020
publisher.none.fl_str_mv Lebanese American University
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spelling Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in LebanonEl Khoury, MariaEnterobacteriaceae -- Molecular aspectsBeta lactam antibioticsDrug resistance in microorganismsEnterobacteriaceae -- LebanonLebanese American University -- DissertationsDissertations, AcademicAntimicrobial resistance is one of the greatest threats to public health. Carbapenems are among the few useful antibiotics against multidrug resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome of clinical carbapenem-resistant Enterobacteriaceae recovered in the period between 2016-2019 from hospitalized patients in Lebanon. The studied population included: 27 Escherichia coli, 24 Klebsiella pneumoniae, one K. quasipneumoniae, three Morganella morganii, three Citrobacter freundii, five Enterobacter hormaechei, and two Serratia marcescens. Antimicrobial susceptibility testing using the disk diffusion assay, carbapenemase confirmatory testing, and in silico whole-genome based analysis revealed that the majority of the isolates (87.7%; n=57) were carbapenem resistant harboring a broad range of carbapenemases. blaOXA-48 (33.8%; n=22) and blaOXA-48-like genes were among the detected resistance determinants, with two isolates additionally co-harboring the blaNDM-5. All OXA-48 producing isolates were ESBL and/or AmpC producers and were additionally resistant to non-β-lactam antibiotics. Carbapenem resistance determinants related to blaNDM were also detected including blaNDM-1 (16.9%; n=11), blaNDM-5 (9.2%; n=6), blaNDM-7 (9.2%; n=6), and blaNDM-19 (4.6%; n=3). A wide variety of ESBLs (OXA, SHV, TEM, CTX-M) and AmpC β-lactamases (CMY, DHA, ACT) were among the detected resistance determinants and of which blaCTX-M-15 (58.5%; n=38) and blaOXA-1 (53.8%; n=35) were the most common. Our study revealed a wide variety of incompatibility groups to be associated with carbapenem resistance with the IncFIB(K) (43.1%; n=28) being the most prevalent, followed by IncFIA (40.0%), IncL (35.4%), IncX3 (32.3%), IncI1 (32.3%), IncFIIK (29.2%). It was also the largest genome-based study in the region, revealing the tremendous heterogeneity, plasmid content, and various resistance determinants circulating in the country. High-risk carbapenem-resistant Enterobacteriaceae clones pose a significant threat to patients and healthcare systems in Lebanon. The observed plethora of plasmid-encoded resistance genes shed light on implementing corrective measures to mitigate the spread of carbapenem resistance.1 online resource (xviii, 89 leaves) : col. ill.Includes bibliographical references (leaf 68-89)Lebanese American University2022-04-11T12:13:39Z2022-04-11T12:13:39Z20202020-07-29Thesisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesishttp://hdl.handle.net/10725/13473https://doi.org/10.26756/th.2022.313http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.phpeninfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/134732022-07-13T09:03:56Z
spellingShingle Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon
El Khoury, Maria
Enterobacteriaceae -- Molecular aspects
Beta lactam antibiotics
Drug resistance in microorganisms
Enterobacteriaceae -- Lebanon
Lebanese American University -- Dissertations
Dissertations, Academic
status_str publishedVersion
title Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon
title_full Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon
title_fullStr Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon
title_full_unstemmed Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon
title_short Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon
title_sort Whole-Genome Sequence Analysis of Carbapenem-Resistant Enterobacteriaceae Recovered from Hospitalized Patients in Lebanon
topic Enterobacteriaceae -- Molecular aspects
Beta lactam antibiotics
Drug resistance in microorganisms
Enterobacteriaceae -- Lebanon
Lebanese American University -- Dissertations
Dissertations, Academic
url http://hdl.handle.net/10725/13473
https://doi.org/10.26756/th.2022.313
http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php