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Genomics And Susceptibility Profiles Of Extensively Drug-resistant Pseudomonas Aeruginosa Isolates From Spain
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This study assessed the molecular epidemiology, resistance mechanisms, and susceptibility profiles of a collection of 150 extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolates obtained from a 2015 Spanish multicenter study, with a particular focus on resistome analysis in relation to ceftolozane-tazobactam susceptibility. Broth microdilution MICs revealed that nearly all (> 95%) of the isolates were nonsusceptible to piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, imipenem, meropenem, and ciprofloxacin. Most of them were also resistant to tobramycin (77%), whereas nonsusceptibility rates were lower for ceftolozane-tazobactam (31%), amikacin (7%), and colistin (2%). Pulsed-field gel electrophoresis-multilocus sequence typing (PFGE-MLST) analysis revealed that nearly all of the isolates belonged to previously described high-risk clones. Sequence type 175 (ST175) was detected in all 9 participating hospitals and accounted for 68% (n = 101) of the XDR isolates, distantly followed by ST244 (n = 16), ST253 (n = 12), ST235 (n = 8), and ST111 (n = 2), which were detected only in 1 to 2 hospitals. Through phenotypic and molecular methods, the presence of horizontally acquired carbapenemases was detected in 21% of the isolates, mostly VIM (17%) and GES enzymes (4%). At least two representative isolates from each clone and hospital (n = 44) were fully sequenced on an illumina MiSeq. Classical mutational mechanisms, such as those leading to the overexpression of the beta-lactamase AmpC or efflux pumps, OprD inactivation, and/or quinolone resistance-determining regions (QRDR) mutations, were confirmed in most isolates and correlated well with the resistance phenotypes in the absence of horizontally acquired determinants. Ceftolozane-tazobactam resistance was not detected in carbapenemase-negative isolates, in agreement with sequencing data showing the absence of ampC mutations. The unique set of mutations responsible for the XDR phenotype of ST175 clone documented 7 years earlier were found to be conserved, denoting the long-term persistence of this specific XDR lineage in Spanish hospitals. Finally, other potentially relevant mutations were evidenced, including those in penicillin-binding protein 3 (PBP3), which is involved in beta-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.
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BARRIO TOFIÑO, Ester, LÓPEZ CAUSAPÉ, Carla, CABOT, Gabriel, RIVERA, Alba, BENITO HERNÁNDEZ, M. natividad de, SEGURA, Concepción, MONTERO, María milagro, SORLI, Luisa, TUBAU, Fe, GÓMEZ-ZORRILLA MARTÍN, Silvia, TORMO, Nuria, DURÁ NAVARRO, Raquel, VIEDMA, Esther, RESINO FOZ, Elena, FERNÁNDEZ MARTÍNEZ, Marta, GONZÁLEZ RICO, Claudia, ALEJO-CANCHO, Izaskun, MARTÍNEZ, José antonio (martínez martínez), LABAYRU ECHVERRIA, Cristina, DUEÑAS, Carlos j., AYESTARAN, Ignacio, ZAMORANO, Laura, MARTÍNEZ MARTÍNEZ, Luis, HORCAJADA GALLEGO, Juan pablo, OLIVER, Antonio. Genomics And Susceptibility Profiles Of Extensively Drug-resistant Pseudomonas Aeruginosa Isolates From Spain. _Antimicrobial Agents And Chemotherapy_. 2017. Vol. 61, núm. 11. [consulta: 15 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/124235]