Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
Journal
Frontiers in Microbiology
ISSN
1664-302X
Date Issued
2022
Author(s)
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
Christian José Pallares
José R. W. Martínez
María Virginia Villegas
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:sec><jats:title>Objectives</jats:title><jats:p>Identify molecular mechanisms responsible for the <jats:italic>in vitro</jats:italic> non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of <jats:italic>Pseudomonas aeruginosa</jats:italic> from five Latin American countries collected before the introduction of TOL into the clinical practice.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Clinical isolates of <jats:italic>P. aeruginosa</jats:italic> (<jats:italic>n</jats:italic> = 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 <jats:italic>bla</jats:italic><jats:sub>KPC</jats:sub>, <jats:italic>bla</jats:italic><jats:sub>NDM-1</jats:sub>, <jats:italic>bla</jats:italic><jats:sub>VIM</jats:sub>, and <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub>. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A 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 <jats:italic>bla</jats:italic><jats:sub>PDC</jats:sub> and <jats:italic>ampD</jats:italic>, associated with decreased susceptibility to TOL.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Substitutions 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.</jats:p></jats:sec>
Cite this document
Mojica, M. F., De La Cadena, E., Ríos, R., García-Betancur, J. C., Díaz, L., Reyes, J., Hernández-Gómez, C., Radice, M., Gales, A. C., Castañeda Méndez, P., Munita, J. M., Pallares, C. J., Martínez, J. R. W., & Villegas, M. V. (2022). Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries. Frontiers in Microbiology, 13, 1035609. https://doi.org/10.3389/fmicb.2022.1035609
Dataset(s)
Dataset - Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries
Subjects
antibiotic resistance
;
ceftolozane/tazobactam
;
latin america
;
molecular mechanisms
;
pseudomonas aeruginosa
;
carbapenemase
;
cefepime
;
ceftazidime
;
ceftolozane plus tazobactam
;
piperacillin plus tazobactam
;
antibiotic resistance
;
antibiotic sensitivity
;
article
;
bacterium identification
;
broth dilution
;
dna extraction
;
matrix assisted laser desorption ionization time of flight mass spectrometry
;
minimum inhibitory concentration
;
multilocus sequence typing
;
nonhuman
;
pangenome
;
phylogenetic tree
;
pseudomonas aeruginosa
;
real time polymerase chain reaction
;
south and central america
;
tree of life
;
whole genome sequencing