RT Journal Article
T1 Genomics and Susceptibility Profiles of Extensively Drug-Resistant Pseudomonas aeruginosa Isolates from Spain
A1 del Barrio-Tofino, Ester
A1 Lopez-Causape, Carla
A1 Cabot, Gabriel
A1 Rivera, Alba
A1 Benito, Natividad
A1 Segura, Concepcion
A1 Milagro Montero, Maria
A1 Sorli, Luisa
A1 Tubau, Fe
A1 Gomez-Zorrilla, Silvia
A1 Tormo, Nuria
A1 Dura-Navarro, Raquel
A1 Viedma, Esther
A1 Resino-Foz, Elena
A1 Fernandez-Martinez, Marta
A1 Gonzalez-Rico, Claudia
A1 Alejo-Cancho, Izaskun
A1 Antonio Martinez, Jose
A1 Labayru-Echverria, Cristina
A1 Duenas, Carlos
A1 Ayestaran, Ignacio
A1 Zamorano, Laura
A1 Martinez-Martinez, Luis
A1 Pablo Horcajada, Juan
A1 Oliver, Antonio
K1 Pseudomonas aeruginosa
K1 whole-genome sequencing
K1 extensively drug resistant
K1 high-risk clones
K1 Field gel-electrophoresis
K1 Beta-lactam resistance
K1 Antimicrobial resistance
K1 Polymyxin resistance
K1 Aminoglycoside resistance
K1 Ceftolozane-tazobactam
K1 Carbapenem resistance
K1 Convergent evolution
K1 Cxa-101 fr264205
K1 Mutations
AB 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.
PB Amer soc microbiology
SN 0066-4804
YR 2017
FD 2017-11-01
LK http://hdl.handle.net/10668/19003
UL http://hdl.handle.net/10668/19003
LA en
DS RISalud
RD Apr 10, 2025