Hernández-García, Marta, García-Castillo, María, García-Fernández, Sergio, Melo-Cristino, José, Pinto, Margarida F, Gonçalves, Elsa, Alves, Valquíria, Vieira, Ana Raquel, Ramalheira, Elmano, Sancho, Luísa, Diogo, José, Ferreira, Rui, Silva, Tânia, Chaves, Catarina, Bou, Germán, Cercenado, Emilia, Delgado-Valverde, Mercedes, Oliver, Antonio, Pitart, Cristina, Rodríguez-Lozano, Jesús, Tormo, Nuria, Romano, João, Pássaro, Leonor, Paixão, Laura, López-Mendoza, Diego, Díaz-Regañón, Jazmín, Cantón, Rafael, Marcelo, Cristina, Peres, Helena, Lourenço, Isabel, Peres, Isabel, Marques, João, Chantre, Odete, Pina, Teresa, Toscano, Cristina, Ribeiro, Manuela, Costa, Eliana, Ferreira, Sónia, Diaz, Raquel, Schäfer, Sandra, Tancredo, Luísa, Rodrigues, Ana, Ramos, Helena, Silva, Daniela, Queiroz, Carolina, Nabiev, Altair, Paixao, Laura, Moura, Carolina, MSD, Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, and European Commission
STEP and SUPERIOR study groups., [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., The study was funded by MSD Portugal (protocol VP6918) and MSD Spain (protocol MSD-CEF-2016-01). This study was also supported by Plan Nacional de I + D + i 2013–16 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 [RD16/0016/0001, RD16/0016/0004, RD16/0016/0006, RD16/0016/0007, RD16/0016/0010 and REIPI RD16/0016/0011], co-financed by the European Development Regional Fund ‘A way to achieve Europe’ (EDRF), Operative Program Intelligent Growth 2014–20. M.H.-G. is supported by a research contract from a European Project [IMI-JU-9–2013, Ref. iABC - 115721–2].