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Genomic Analysis of Ceftazidime/Avibactam-Resistant GES-Producing Sequence Type 235 <i>Pseudomonas aeruginosa</i> Isolates

The emergence of ceftazidime/avibactam (CZA) resistance among Guiana extended-spectrum <i>β</i>-lactamase (GES)-producing <i>Pseudomonas aeruginosa</i> isolates has rarely been described. Herein, we analyze the phenotypic and genomic characterization of CZA resistance in diff...

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Main Authors: Raúl Recio (Author), Jennifer Villa (Author), Sara González-Bodí (Author), Patricia Brañas (Author), María Ángeles Orellana (Author), Mikel Mancheño-Losa (Author), Jaime Lora-Tamayo (Author), Fernando Chaves (Author), Esther Viedma (Author)
Format: Book
Published: MDPI AG, 2022-06-01T00:00:00Z.
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Summary:The emergence of ceftazidime/avibactam (CZA) resistance among Guiana extended-spectrum <i>β</i>-lactamase (GES)-producing <i>Pseudomonas aeruginosa</i> isolates has rarely been described. Herein, we analyze the phenotypic and genomic characterization of CZA resistance in different GES-producing <i>P. aeruginosa</i> isolates that emerged in our institution. A subset of nine CZA-resistant <i>P. aeruginosa</i> isolates was analyzed and compared with thirteen CZA-susceptible isolates by whole-genome sequencing (WGS). All CZA-resistant isolates belonged to the ST235 clone and O11 serotype. A variety of GES enzymes were detected: GES-20 (55.6%, 5/9), GES-5 (22.2%, 2/9), GES-1 (11.1%, 1/9), and GES-7 (11.1%, 1/9). WGS revealed the presence of two mutations within the <i>bla</i><sub>GES-20</sub> gene comprising two single-nucleotide substitutions, which caused aspartic acid/serine and leucine/premature stop codon amino acid changes at positions 165 (D165S) and 237 (L237X), respectively. No major differences in the mutational resistome (AmpC, OprD porin, and MexAB-OprM efflux pump-encoding genes) were found among CZA-resistant and CZA-susceptible isolates. None of the mutations that have been previously demonstrated to cause CZA resistance were observed. Different mutations within the <i>bla</i><sub>GES-20</sub> gene were documented in CZA-resistant GES-producing <i>P. aeruginosa</i> isolates belonging to the ST235 clone in our institution. Although further analysis should be performed, according to our results, other resistance mechanisms might be involved in CZA resistance.
Item Description:10.3390/antibiotics11070871
2079-6382

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