Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa

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dc.contributor.authorSoto, Katherine D.
dc.contributor.authorAlcalde-Rico, Manuel
dc.contributor.authorUgalde, Juan A.
dc.contributor.authorOlivares-Pacheco, Jorge
dc.contributor.authorQuiroz, Valeria
dc.contributor.authorBrito, Bárbara
dc.contributor.authorRivas, Lina M.
dc.contributor.authorMunita, José M.
dc.contributor.authorGarcía, Patricia C.
dc.contributor.authorWozniak, Aniela
dc.date.accessioned2024-07-19T15:48:31Z
dc.date.available2024-07-19T15:48:31Z
dc.date.issued2024
dc.descriptionIndexación: Scopus.
dc.description.abstractIntroduction: Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant Pseudomonas aeruginosa, particularly those that are carbapenem resistant. CZA resistance in P. aeruginosa producing PER, a class A extended-spectrum β-lactamase, has been well documented in vitro. However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing P. aeruginosa clinical isolates that were ceftazidime and/or carbapenem non-susceptible. Methods: Antimicrobial susceptibility was determined through agar dilution and broth microdilution, while blaPER gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of blaPER-3 gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics. Results: Twenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried blaPER. One isolate carried blaPER but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their blaPER-3 gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum β-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of blaPER-3 gene restored susceptibility to CZA, ceftolozane/tazobactam and other β-lactamsin the in vitro evolved isolate. Discussion: PER-3-producing ST309 P. aeruginosa is a successful multidrug-resistant clone with blaPER-3 gene implicated in resistance to CZA and other β-lactams.
dc.description.urihttps://www-scopus-com.recursosbiblioteca.unab.cl/record/display.uri?eid=2-s2.0-85196292950&origin=resultslist&sort=plf-f&src=s&nlo=&nlr=&nls=&sid=dbd85ca00ec1299adff19f78e4cdb00d&sot=aff&sdt=cl&cluster=scofreetoread%2c%22all%22%2ct&sl=34&s=AF-ID%2860002636%29+AND+SUBJAREA%28IMMU%29&relpos=18&citeCnt=0&searchTerm=
dc.identifier.citationFrontiers in Cellular and Infection Microbiology Open Access Volume 142024 Article number 1410834
dc.identifier.doi10.3389/fcimb.2024.1410834
dc.identifier.issn22352988
dc.identifier.urihttps://repositorio.unab.cl/handle/ria/58606
dc.language.isoen
dc.publisherFrontiers Media SA
dc.rights.licenseCC BY 4.0 ATTRIBUTION 4.0 INTERNATIONAL
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectblaPER-3 gene
dc.subjectceftazidime/avibactam resistance
dc.subjectmutations conferring CZA resistance
dc.subjectPER-3 extended-spectrum β-lactamase
dc.subjectPseudomonas aeruginosa
dc.titleCeftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa
dc.typeArtículo
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