Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples

<b>Background/Objectives</b>: Infections caused by multidrug-resistant (MDR)bacteria pose a significant public health threat by worsening patient outcomes, contributing to hospital outbreaks, and increasing health and economic burdens. Advanced genomic tools enhance the detection of resi...

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Main Authors: Alexander Tristancho-Baró, Laura Eva Franco-Fobe, Monica Pilar Ariza, Ana Milagro, Ana Isabel López-Calleja, Blanca Fortuño, Concepción López, Miriam Latorre-Millán, Laura Clusa, Rosa Martínez, Carmen Torres, Antonio Rezusta
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Language:English
Published: MDPI AG 2025-01-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/1/42
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author Alexander Tristancho-Baró
Laura Eva Franco-Fobe
Monica Pilar Ariza
Ana Milagro
Ana Isabel López-Calleja
Blanca Fortuño
Concepción López
Miriam Latorre-Millán
Laura Clusa
Rosa Martínez
Carmen Torres
Antonio Rezusta
author_facet Alexander Tristancho-Baró
Laura Eva Franco-Fobe
Monica Pilar Ariza
Ana Milagro
Ana Isabel López-Calleja
Blanca Fortuño
Concepción López
Miriam Latorre-Millán
Laura Clusa
Rosa Martínez
Carmen Torres
Antonio Rezusta
author_sort Alexander Tristancho-Baró
collection DOAJ
description <b>Background/Objectives</b>: Infections caused by multidrug-resistant (MDR)bacteria pose a significant public health threat by worsening patient outcomes, contributing to hospital outbreaks, and increasing health and economic burdens. Advanced genomic tools enhance the detection of resistance genes, virulence factors, and high-risk clones, thus improving the management of MDR infections. In the Autonomous Community of Aragon, the diversity and incidence of carbapenemase-producing Enterobacteriaceae (CPE) have increased during the last years. This study analyses CPE trends at a tertiary hospital in Spain from 2021 to 2023, aiming to optimize personalized medicine. <b>Methods</b>: CPE isolates were the first isolate per patient, year, species, and carbapenemase from January 2021 to December 2023. Additional metadata were collected from the laboratory’s information system. Antibiotic susceptibility testing was performed by broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina short reads. De novo assembly was used to generate draft genomes in order to determine their complete taxonomic classification, resistome, plasmidome, sequence type (ST), core–genome multilocus sequence typing (cgMLST), and phylogenetic relationships using a suite of bioinformatics tools and in-house scripts. <b>Results</b>: Between 2021 and 2023, 0.4% out of 38,145 Enterobacteriaceae isolates were CPE. The CPE rate tripled in 2022 and doubled again in 2023. The most common species was <i>Klebsiella pneumoniae</i> (51.8%) and the most common carbapenemase was <i>bla<sub>OXA-48</sub></i>. WGS revealed concordant species identification and the carbapenemase distribution in detail. Resistance rates to critical antibiotics, such as carbapenems, were variable, but in most cases were above 70%. Genetic diversity was observed in WGS and phylogenetic analyses, with plasmids often mediating carbapenemase dissemination. <b>Conclusions</b>: The increasing rate of CPE in healthcare settings highlights a critical public health challenge, with limited treatment options. Genomic characterization is essential to understanding resistance mechanisms, aiding therapy, limiting outbreaks, and improving precision medicine.
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spelling doaj-art-45b96fa786624cbc9215a3a4ef934c552025-01-24T13:18:42ZengMDPI AGAntibiotics2079-63822025-01-011414210.3390/antibiotics14010042Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human SamplesAlexander Tristancho-Baró0Laura Eva Franco-Fobe1Monica Pilar Ariza2Ana Milagro3Ana Isabel López-Calleja4Blanca Fortuño5Concepción López6Miriam Latorre-Millán7Laura Clusa8Rosa Martínez9Carmen Torres10Antonio Rezusta11Clinical Microbiology Laboratory, Miguel Servet University Hospital, 50009 Zaragoza, SpainClinical Microbiology Laboratory, Miguel Servet University Hospital, 50009 Zaragoza, SpainClinical Microbiology Laboratory, Miguel Servet University Hospital, 50009 Zaragoza, SpainClinical Microbiology Laboratory, Miguel Servet University Hospital, 50009 Zaragoza, SpainClinical Microbiology Laboratory, Miguel Servet University Hospital, 50009 Zaragoza, SpainClinical Microbiology Laboratory, Miguel Servet University Hospital, 50009 Zaragoza, SpainClinical Microbiology Laboratory, Miguel Servet University Hospital, 50009 Zaragoza, SpainResearch Group on Difficult to Diagnose and Treat Infections, Institute for Health Research Aragon, Miguel Servet University Hospital, 50009 Zaragoza, SpainResearch Group on Difficult to Diagnose and Treat Infections, Institute for Health Research Aragon, Miguel Servet University Hospital, 50009 Zaragoza, SpainInfectious Diseases Department, Miguel Servet University Hospital, 50009 Zaragoza, SpainArea of Biochemistry and Molecular Biology, One Health-UR Research Group, University of La Rioja, 26006 Logroño, SpainClinical Microbiology Laboratory, Miguel Servet University Hospital, 50009 Zaragoza, Spain<b>Background/Objectives</b>: Infections caused by multidrug-resistant (MDR)bacteria pose a significant public health threat by worsening patient outcomes, contributing to hospital outbreaks, and increasing health and economic burdens. Advanced genomic tools enhance the detection of resistance genes, virulence factors, and high-risk clones, thus improving the management of MDR infections. In the Autonomous Community of Aragon, the diversity and incidence of carbapenemase-producing Enterobacteriaceae (CPE) have increased during the last years. This study analyses CPE trends at a tertiary hospital in Spain from 2021 to 2023, aiming to optimize personalized medicine. <b>Methods</b>: CPE isolates were the first isolate per patient, year, species, and carbapenemase from January 2021 to December 2023. Additional metadata were collected from the laboratory’s information system. Antibiotic susceptibility testing was performed by broth microdilution. Whole-genome sequencing (WGS) was performed using Illumina short reads. De novo assembly was used to generate draft genomes in order to determine their complete taxonomic classification, resistome, plasmidome, sequence type (ST), core–genome multilocus sequence typing (cgMLST), and phylogenetic relationships using a suite of bioinformatics tools and in-house scripts. <b>Results</b>: Between 2021 and 2023, 0.4% out of 38,145 Enterobacteriaceae isolates were CPE. The CPE rate tripled in 2022 and doubled again in 2023. The most common species was <i>Klebsiella pneumoniae</i> (51.8%) and the most common carbapenemase was <i>bla<sub>OXA-48</sub></i>. WGS revealed concordant species identification and the carbapenemase distribution in detail. Resistance rates to critical antibiotics, such as carbapenems, were variable, but in most cases were above 70%. Genetic diversity was observed in WGS and phylogenetic analyses, with plasmids often mediating carbapenemase dissemination. <b>Conclusions</b>: The increasing rate of CPE in healthcare settings highlights a critical public health challenge, with limited treatment options. Genomic characterization is essential to understanding resistance mechanisms, aiding therapy, limiting outbreaks, and improving precision medicine.https://www.mdpi.com/2079-6382/14/1/42carbapenem-resistant enterobacteriaceaewhole-genome sequencingdrug resistancemicrobialcomputational biology
spellingShingle Alexander Tristancho-Baró
Laura Eva Franco-Fobe
Monica Pilar Ariza
Ana Milagro
Ana Isabel López-Calleja
Blanca Fortuño
Concepción López
Miriam Latorre-Millán
Laura Clusa
Rosa Martínez
Carmen Torres
Antonio Rezusta
Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples
Antibiotics
carbapenem-resistant enterobacteriaceae
whole-genome sequencing
drug resistance
microbial
computational biology
title Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples
title_full Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples
title_fullStr Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples
title_full_unstemmed Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples
title_short Genomic Characterization of Carbapenemase-Producing Enterobacteriaceae from Clinical and Epidemiological Human Samples
title_sort genomic characterization of carbapenemase producing enterobacteriaceae from clinical and epidemiological human samples
topic carbapenem-resistant enterobacteriaceae
whole-genome sequencing
drug resistance
microbial
computational biology
url https://www.mdpi.com/2079-6382/14/1/42
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