%0 Journal Article
%A del Barrio-Tofino, Ester
%A Lopez-Causape, Carla
%A Cabot, Gabriel
%A Rivera, Alba
%A Benito, Natividad
%A Segura, Concepcion
%A Milagro Montero, Maria
%A Sorli, Luisa
%A Tubau, Fe
%A Gomez-Zorrilla, Silvia
%A Tormo, Nuria
%A Dura-Navarro, Raquel
%A Viedma, Esther
%A Resino-Foz, Elena
%A Fernandez-Martinez, Marta
%A Gonzalez-Rico, Claudia
%A Alejo-Cancho, Izaskun
%A Antonio Martinez, Jose
%A Labayru-Echverria, Cristina
%A Duenas, Carlos
%A Ayestaran, Ignacio
%A Zamorano, Laura
%A Martinez-Martinez, Luis
%A Pablo Horcajada, Juan
%A Oliver, Antonio
%T Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain
%D 2017
%@ 0066-4804
%U http://hdl.handle.net/10668/19003
%X 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.
%K Pseudomonas aeruginosa
%K whole-genome sequencing
%K extensively drug resistant
%K high-risk clones
%K Field gel-electrophoresis
%K Beta-lactam resistance
%K Antimicrobial resistance
%K Polymyxin resistance
%K Aminoglycoside resistance
%K Ceftolozane-tazobactam
%K Carbapenem resistance
%K Convergent evolution
%K Cxa-101 fr264205
%K Mutations
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