Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries

ObjectivesIdentify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice.MethodsClinical...

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發表在:Frontiers in Microbiology
Main Authors: María F. Mojica, Elsa De La Cadena, Rafael Ríos, Juan Carlos García-Betancur, Lorena Díaz, Jinnethe Reyes, Cristhian Hernández-Gómez, Marcela Radice, Ana C. Gales, Paulo Castañeda Méndez, José M. Munita, Christian José Pallares, José R. W. Martínez, María Virginia Villegas
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語言:英语
出版: Frontiers Media S.A. 2022-10-01
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在線閱讀:https://www.frontiersin.org/articles/10.3389/fmicb.2022.1035609/full
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author María F. Mojica
María F. Mojica
María F. Mojica
María F. Mojica
Elsa De La Cadena
Rafael Ríos
Juan Carlos García-Betancur
Lorena Díaz
Lorena Díaz
Jinnethe Reyes
Cristhian Hernández-Gómez
Marcela Radice
Marcela Radice
Ana C. Gales
Paulo Castañeda Méndez
José M. Munita
José M. Munita
Christian José Pallares
Christian José Pallares
José R. W. Martínez
José R. W. Martínez
María Virginia Villegas
María Virginia Villegas
author_facet María F. Mojica
María F. Mojica
María F. Mojica
María F. Mojica
Elsa De La Cadena
Rafael Ríos
Juan Carlos García-Betancur
Lorena Díaz
Lorena Díaz
Jinnethe Reyes
Cristhian Hernández-Gómez
Marcela Radice
Marcela Radice
Ana C. Gales
Paulo Castañeda Méndez
José M. Munita
José M. Munita
Christian José Pallares
Christian José Pallares
José R. W. Martínez
José R. W. Martínez
María Virginia Villegas
María Virginia Villegas
author_sort María F. Mojica
collection DOAJ
container_title Frontiers in Microbiology
description ObjectivesIdentify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice.MethodsClinical isolates of P. aeruginosa (n = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect blaKPC, blaNDM-1, blaVIM, and blaIMP. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases.ResultsA total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated blaPDC and ampD, associated with decreased susceptibility to TOL.ConclusionSubstitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.
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spelling doaj-art-bad2ea52247c4e068b84db4d0044bbb62025-08-19T21:22:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-10-011310.3389/fmicb.2022.10356091035609Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countriesMaría F. Mojica0María F. Mojica1María F. Mojica2María F. Mojica3Elsa De La Cadena4Rafael Ríos5Juan Carlos García-Betancur6Lorena Díaz7Lorena Díaz8Jinnethe Reyes9Cristhian Hernández-Gómez10Marcela Radice11Marcela Radice12Ana C. Gales13Paulo Castañeda Méndez14José M. Munita15José M. Munita16Christian José Pallares17Christian José Pallares18José R. W. Martínez19José R. W. Martínez20María Virginia Villegas21María Virginia Villegas22Grupo de Investigación en Resistencia Antimicrobiana y Epidemiologia Hospitalaria, Universidad El Bosque, Bogotá, ColombiaDepartment of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, Cleveland, OH, United StatesCleveland VA Medical Center for Antimicrobial Resistance and Epidemiology (Case VA CARES), Case Western Reserve University, Cleveland, OH, United StatesResearch Service, VA Northeast Ohio Healthcare System, Cleveland, OH, United StatesGrupo de Investigación en Resistencia Antimicrobiana y Epidemiologia Hospitalaria, Universidad El Bosque, Bogotá, ColombiaMolecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, ColombiaGrupo de Investigación en Resistencia Antimicrobiana y Epidemiologia Hospitalaria, Universidad El Bosque, Bogotá, ColombiaMolecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, ColombiaMillenium Initiative for Collaborative Research on Bacterial Resistance (MICROB-R), Santiago, ChileMolecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogotá, ColombiaGrupo de Investigación en Resistencia Antimicrobiana y Epidemiologia Hospitalaria, Universidad El Bosque, Bogotá, ColombiaUniversidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Buenos Aires, ArgentinaConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, ArgentinaUniversidade Federal de São Paulo, Division of Infectious Diseases, Brazil0Hospital Médica Sur, Ciudad de México, MexicoMillenium Initiative for Collaborative Research on Bacterial Resistance (MICROB-R), Santiago, Chile1Genomics and Resistant Microbes (GeRM) Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, ChileGrupo de Investigación en Resistencia Antimicrobiana y Epidemiologia Hospitalaria, Universidad El Bosque, Bogotá, Colombia2Clínica Imbanaco, Grupo Quiron, Cali, ColombiaMillenium Initiative for Collaborative Research on Bacterial Resistance (MICROB-R), Santiago, Chile1Genomics and Resistant Microbes (GeRM) Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Clínica Alemana, Universidad del Desarrollo, Santiago, ChileGrupo de Investigación en Resistencia Antimicrobiana y Epidemiologia Hospitalaria, Universidad El Bosque, Bogotá, Colombia2Clínica Imbanaco, Grupo Quiron, Cali, ColombiaObjectivesIdentify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice.MethodsClinical isolates of P. aeruginosa (n = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect blaKPC, blaNDM-1, blaVIM, and blaIMP. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases.ResultsA total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated blaPDC and ampD, associated with decreased susceptibility to TOL.ConclusionSubstitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1035609/fullceftolozane/tazobactamPseudomonas aeruginosaantibiotic resistancemolecular mechanismsLatin America
spellingShingle María F. Mojica
María F. Mojica
María F. Mojica
María F. Mojica
Elsa De La Cadena
Rafael Ríos
Juan Carlos García-Betancur
Lorena Díaz
Lorena Díaz
Jinnethe Reyes
Cristhian Hernández-Gómez
Marcela Radice
Marcela Radice
Ana C. Gales
Paulo Castañeda Méndez
José M. Munita
José M. Munita
Christian José Pallares
Christian José Pallares
José R. W. Martínez
José R. W. Martínez
María Virginia Villegas
María Virginia Villegas
Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
ceftolozane/tazobactam
Pseudomonas aeruginosa
antibiotic resistance
molecular mechanisms
Latin America
title Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
title_full Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
title_fullStr Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
title_full_unstemmed Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
title_short Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
title_sort molecular mechanisms leading to ceftolozane tazobactam resistance in clinical isolates of pseudomonas aeruginosa from five latin american countries
topic ceftolozane/tazobactam
Pseudomonas aeruginosa
antibiotic resistance
molecular mechanisms
Latin America
url https://www.frontiersin.org/articles/10.3389/fmicb.2022.1035609/full
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