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. 2022 Oct 28;77(11):3163-3172.
doi: 10.1093/jac/dkac298.

In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal (SUPERIOR and STEP studies)

Marta Hernández-García  1   2 , María García-Castillo  1 , José Melo-Cristino  3 , Margarida F Pinto  4 , Elsa Gonçalves  5 , Valquíria Alves  6 , Ana Raquel Vieira  7 , Elmano Ramalheira  8 , Luísa Sancho  9 , José Diogo  10 , Rui Ferreira  11 , Hugo Cruz  12 , Catarina Chaves  13 , Germán Bou  2   14 , Emilia Cercenado  15   16 , Mercedes Delgado-Valverde  2   17 , Antonio Oliver  2   18 , Cristina Pitart  19 , Jesús Rodríguez-Lozano  20 , Nuria Tormo  21 , Jazmín Díaz-Regañón  22 , Leonor Pássaro  23 , Joana Duarte  23 , Rafael Cantón  1   2 ; STEP and SUPERIOR study groups
Collaborators, Affiliations

In vitro activity of imipenem/relebactam against Pseudomonas aeruginosa isolates recovered from ICU patients in Spain and Portugal (SUPERIOR and STEP studies)

Marta Hernández-García et al. J Antimicrob Chemother. .

Abstract

Objectives: To study the in vitro activity of imipenem/relebactam and comparators and the imipenem/relebactam resistance mechanisms in a Pseudomonas aeruginosa collection from Portugal (STEP, 2017-18) and Spain (SUPERIOR, 2016-17) surveillance studies.

Methods: P. aeruginosa isolates (n = 474) were prospectively recovered from complicated urinary tract (cUTI), complicated intra-abdominal (cIAI) and lower respiratory tract (LRTI) infections in 11 Portuguese and 8 Spanish ICUs. MICs were determined (ISO broth microdilution). All imipenem/relebactam-resistant P. aeruginosa isolates (n = 30) and a subset of imipenem/relebactam-susceptible strains (n = 32) were characterized by WGS.

Results: Imipenem/relebactam (93.7% susceptible), ceftazidime/avibactam (93.5% susceptible) and ceftolozane/tazobactam (93.2% susceptible) displayed comparable activity. The imipenem/relebactam resistance rate was 6.3% (Portugal 5.8%; Spain 8.9%). Relebactam restored imipenem susceptibility to 76.9% (103/134) of imipenem-resistant isolates, including MDR (82.1%; 32/39), XDR (68.8%; 53/77) and difficult-to-treat (DTR) isolates (67.2%; 45/67). Among sequenced strains, differences in population structure were detected depending on the country: clonal complex (CC)175 and CC309 in Spain and CC235, CC244, CC348 and CC253 in Portugal. Different carbapenemase gene distributions were also found: VIM-20 (n = 3), VIM-1 (n = 2), VIM-2 (n = 1) and VIM-36 (n = 1) in Spain and GES-13 (n = 13), VIM-2 (n = 3) and KPC-3 (n = 2) in Portugal. GES-13-CC235 (n = 13) and VIM type-CC175 (n = 5) associations were predominant in Portugal and Spain, respectively. Imipenem/relebactam showed activity against KPC-3 strains (2/2), but was inactive against all GES-13 producers and most of the VIM producers (8/10). Mutations in genes affecting porin inactivation, efflux pump overexpression and LPS modification might also be involved in imipenem/relebactam resistance.

Conclusions: Microbiological results reinforce imipenem/relebactam as a potential option to treat cUTI, cIAI and LRTI caused by MDR/XDR P. aeruginosa isolates, except for GES-13 and VIM producers.

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