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Title: Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain.
Authors: Del Barrio-Tofiño, Ester
López-Causapé, Carla
Cabot, Gabriel
Rivera, Alba
Benito, Natividad
Segura, Concepción
Montero, María Milagro
Sorlí, Luisa
Tubau, Fe
Gómez-Zorrilla, Silvia
Tormo, Nuria
Durá-Navarro, Raquel
Viedma, Esther
Resino-Foz, Elena
Fernández-Martínez, Marta
González-Rico, Claudia
Alejo-Cancho, Izaskun
Martínez, Jose Antonio
Labayru-Echverria, Cristina
Dueñas, Carlos
Ayestarán, Ignacio
Zamorano, Laura
Martinez-Martinez, Luis
Horcajada, Juan Pablo
Oliver, Antonio
Keywords: Pseudomonas aeruginosa;extensively drug resistant;high-risk clones;whole-genome sequencing
metadata.dc.subject.mesh: Aminoglycosides
Anti-Bacterial Agents
Bacterial Proteins
Drug Resistance, Bacterial
Microbial Sensitivity Tests
Molecular Epidemiology
Penicillanic Acid
Pseudomonas Infections
Pseudomonas aeruginosa
beta-Lactam Resistance
Issue Date: 24-Oct-2017
Abstract: 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 β-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 β-lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.
metadata.dc.identifier.doi: 10.1128/AAC.01589-17
Appears in Collections:Producción 2020

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