Hernández-García, MartaGarcía-Castillo, MaríaGarcía-Fernández, SergioMelo-Cristino, JoséPinto, Margarida FeijóGonçalves, ElsaAlves, ValquíriaVieira, Ana RaquelRamalheira, ElmanoSancho, LuísaDiogo, JoséFerreira, RuiSilva, TaniaChaves, CatarinaBou, GermánCercenado, EmiliaDelgado-Valverde, MercedesOliver, AntonioPitart, CristinaRodríguez-Lozano, JesúsTormo, NuriaRomano, JoaoPássaro, LeonorPaixao, LauraLópez-Mendoza, DiegoDíaz-Regañón, JazmínCantón, Rafael2025-10-302025-10-302020-10-25Hernández-García M, García-Castillo M, García-Fernández S, Melo-Cristino J, Pinto MF, Gonçalves E, Alves V, Vieira AR, Ramalheira E, Sancho L, Diogo J, Ferreira R, Silva T, Chaves C, Bou G, Cercenado E, Delgado-Valverde M, Oliver A, Pitart C, Rodríguez-Lozano J, Tormo N, Romano J, Pássaro L, Paixão L, López-Mendoza D, Díaz-Regañón J, Cantón R; STEP and SUPERIOR study groups. Distinct epidemiology and resistance mechanisms affecting ceftolozane/tazobactam in Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal depicted by WGS. J Antimicrob Chemother. 2021 Jan 19;76(2):370-379.0305-7453https://hdl.handle.net/2183/46187[Abstract] Objectives: To analyse the epidemiology, the resistome and the virulome of ceftolozane/tazobactam-susceptible or -resistant Pseudomonas aeruginosa clinical isolates recovered from surveillance studies in Portugal (STEP, 2017-18) and Spain (SUPERIOR, 2016-17). Methods: P. aeruginosa isolates were recovered from intra-abdominal, urinary tract and lower respiratory tract infections in ICU patients admitted to 11 Portuguese and 8 Spanish hospitals. MICs were determined (ISO-standard broth microdilution, EUCAST 2020 breakpoints). A subset of 28 ceftolozane/tazobactam-resistant P. aeruginosa isolates were analysed and compared with 28 ceftolozane/tazobactam-susceptible P. aeruginosa strains by WGS. Results: Clonal complex (CC) 235 (27%) and CC175 (18%) were the most frequent, followed by CC244 (13%), CC348 (9%), CC253 (5%) and CC309 (5%). Inter-hospital clonal dissemination was observed, limited to a geographical region (CC235, CC244, CC348 and CC253 in Portugal and CC175 and CC309 in Spain). Carbapenemases were detected in 25 isolates (45%): GES-13 (13/25); VIM type (10/25) [VIM-2 (4/10), VIM-20 (3/10), VIM-1 (2/10) and VIM-36 (1/10)]; and KPC-3 (2/25). GES-13-CC235 (13/15) and VIM type-CC175 (5/10) associations were observed. Interestingly, KPC-3 and VIM-36 producers showed ceftolozane/tazobactam-susceptible phenotypes. However, ceftolozane/tazobactam resistance was significantly associated with GES-13 and VIM-type carbapenemase production. Six non-carbapenemase producers also displayed ceftolozane/tazobactam resistance, three of them showing known ceftolozane/tazobactam resistance-associated mutations in the PBP3 gene, ftsI (R504C and F533L). Overall, an extensive virulome was identified in all P. aeruginosa isolates, particularly in carbapenemase-producing strains. Conclusions: GES-13-CC235 and VIM type-CC175 were the most frequent MDR/XDR P. aeruginosa clones causing infections in Portuguese and Spanish ICU patients, respectively. Ceftolozane/tazobactam resistance was mainly due to carbapenemase production, although mutations in PBP-encoding genes may additionally be involved.engThis is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Antimicrobial Chemotherapy following peer review. The version of record is available online at Oxford Academic web page.Pseudomonas infectionsPseudomonas aeruginosajournal articleopen access10.1093/jac/dkaa430