Distinct epidemiology and resistance mechanisms affecting ceftolozane/tazobactam inPseudomonas aeruginosaisolates recovered from ICU patients in Spain and Portugal depicted by WGS
Authors: 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 ,   the STEP and SUPERIOR study groups, Melo-Cristino José , Pinto Margarida F , Marcelo Cristina , Peres Helena , Lourenço Isabel , Peres Isabel , Marques João , Chantre Odete , Pina Teresa , Gonçalves Elsa , Toscano Cristina , Alves Valquíria , Ribeiro Manuela , Costa Eliana , Vieira Ana Raquel , Ferreira Sónia , Diaz Raquel , Ramalheira Elmano , Schäfer Sandra , Tancredo Luísa , Sancho Luísa , Rodrigues Ana , Diogo José , Ferreira Rui , Ramos Helena , Silva Tânia , Silva Daniela , Chaves Catarina , Queiroz Carolina , Nabiev Altair , Pássaro Leonor , Paixao Laura , Romano João , Moura Carolina 
Published: September 2020

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.