AUTHOR=Mojica María F. , De La Cadena Elsa , Ríos Rafael , García-Betancur Juan Carlos , Díaz Lorena , Reyes Jinnethe , Hernández-Gómez Cristhian , Radice Marcela , Gales Ana C. , Castañeda Méndez Paulo , Munita José M. , Pallares Christian José , Martínez José R. W. , Villegas María Virginia 

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

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.1035609

DOI=10.3389/fmicb.2022.1035609

ISSN=1664-302X

ABSTRACT=<sec><title>Objectives</title><p>Identify molecular mechanisms responsible for the <italic>in vitro</italic> non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of <italic>Pseudomonas aeruginosa</italic> from five Latin American countries collected before the introduction of TOL into the clinical practice.</p></sec><sec><title>Methods</title><p>Clinical isolates of <italic>P. aeruginosa</italic> (<italic>n</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 <italic>bla</italic><sub>KPC</sub>, <italic>bla</italic><sub>NDM-1</sub>, <italic>bla</italic><sub>VIM</sub>, and <italic>bla</italic><sub>IMP</sub>. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases.</p></sec><sec><title>Results</title><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 <italic>bla</italic><sub>PDC</sub> and <italic>ampD</italic>, associated with decreased susceptibility to TOL.</p></sec><sec><title>Conclusion</title><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.</p></sec>