Genomics and susceptibility profiles of extensively drug-resistant pseudomonas aeruginosa isolates from Spain

Ester Del Barrio-Tofiño, Carla López-Causapé, Gabriel Cabot, Alba Rivera, Natividad Benito, Concepción Segura, María Milagro Montero, Luisa Sorlí, Fe Tubau, Silvia Gómez-Zorrilla, Nuria Tormo, Raquel Durá-Navarro, Esther Viedma, Elena Resino-Foz, Marta Fernández-Martínez, Claudia González-Rico, Izaskun Alejo-Cancho, Jose Antonio Martínez, Cristina Labayru-Echverria, Carlos DueñasIgnacio Ayestarán, Laura Zamorano, Luis Martinez-Martinez, Juan Pablo Horcajada, Antonio Oliver*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

75 Citations (Scopus)


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.

Original languageAmerican English
Article numbere01589-17
JournalAntimicrobial Agents and Chemotherapy
Issue number11
Publication statusPublished - Nov 2017


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