Publication: Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa
dc.contributor.author | Soto, Katherine | |
dc.contributor.author | Alcalde, Manuel | |
dc.contributor.author | Ugalde, Juan | |
dc.contributor.author | Olivares, Jorge | |
dc.contributor.author | Quiroz, Valeria | |
dc.contributor.author | Brito, Bárbara | |
dc.contributor.author | Rivas Jiménez, Lina María | |
dc.contributor.author | Munita, Jose M. | |
dc.contributor.author | García, Patricia | |
dc.contributor.author | Wozniak, Aniela | |
dc.date.accessioned | 2025-01-16T13:39:23Z | |
dc.date.available | 2025-01-16T13:39:23Z | |
dc.date.issued | 2024 | |
dc.description.abstract | Introduction: 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 bla PER 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 bla PER-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 bla PER. One isolate carried bla PER 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 bla PER-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 bla PER-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.version | Versión Publicada | |
dc.identifier.citation | Soto KD, Alcalde-Rico M, Ugalde JA, Olivares-Pacheco J, Quiroz V, Brito B, Rivas LM, Munita JM, García PC, Wozniak A. Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa. Front Cell Infect Microbiol. 2024 Jun 5;14:1410834. doi: 10.3389/fcimb.2024.1410834 | |
dc.identifier.doi | https://doi.org/10.3389/fcimb.2024.1410834 | |
dc.identifier.uri | https://hdl.handle.net/11447/9660 | |
dc.language.iso | en | |
dc.subject | PER-3 extended-spectrum β-lactamase | |
dc.subject | Pseudomonas aeruginosa | |
dc.subject | BlaPER-3 gene | |
dc.subject | Ceftazidime/avibactam resistance | |
dc.subject | Mutations Conferring CZA resistance | |
dc.title | Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa | |
dc.type | Article | |
dcterms.accessRights | Acceso Abierto | |
dcterms.source | Frontiers in cellular and infection microbiology | |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | 2bf16b44-04d3-45fe-8dd0-dafa6322ca94 | |
relation.isAuthorOfPublication | ec52b0bf-d0bc-4844-9531-eca4a65f2b8e | |
relation.isAuthorOfPublication.latestForDiscovery | 2bf16b44-04d3-45fe-8dd0-dafa6322ca94 |
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