TY - JOUR
T1 - Genomics and susceptibility profiles of extensively drug-resistant pseudomonas aeruginosa isolates from Spain
AU - Del Barrio-Tofiño, Ester
AU - López-Causapé, Carla
AU - Cabot, Gabriel
AU - Rivera, Alba
AU - Benito, Natividad
AU - Segura, Concepción
AU - Montero, María Milagro
AU - Sorlí, Luisa
AU - Tubau, Fe
AU - Gómez-Zorrilla, Silvia
AU - Tormo, Nuria
AU - Durá-Navarro, Raquel
AU - Viedma, Esther
AU - Resino-Foz, Elena
AU - Fernández-Martínez, Marta
AU - González-Rico, Claudia
AU - Alejo-Cancho, Izaskun
AU - Martínez, Jose Antonio
AU - Labayru-Echverria, Cristina
AU - Dueñas, Carlos
AU - Ayestarán, Ignacio
AU - Zamorano, Laura
AU - Martinez-Martinez, Luis
AU - Horcajada, Juan Pablo
AU - Oliver, Antonio
N1 - Funding Information:
This work was supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (grants REIPI RD16/0016/0002, RD16/0016/0004 RD16/0016/0005, RD16/0016/0007, RD16/0016/0008, RD16/0016/0010, and RD16/0016/0015), and grants PI15/00088 (PI AO) and PI13/00984 (PI JPH) cofinanced by European Development Regional Fund (ERDF) “A way to achieve Europe,” Operative program Intelligent Growth 2014-2020.
Publisher Copyright:
Copyright © 2017 American Society for Microbiology. All Rights Reserved.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2017/11
Y1 - 2017/11
N2 - 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 -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 -lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.
AB - 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 -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 -lactam (including ceftolozane-tazobactam) resistance, and FusA1, which is linked to aminoglycoside resistance.
UR - http://www.scopus.com/inward/record.url?scp=85032468119&partnerID=8YFLogxK
U2 - 10.1128/AAC.01589-17
DO - 10.1128/AAC.01589-17
M3 - Artículo
C2 - 28874376
AN - SCOPUS:85032468119
VL - 61
IS - 11
M1 - e01589-17
ER -