Activity of ceftolozane/tazobactam and imipenem/relebactam against Gram-negative clinical isolates collected in Mexico—SMART 2017–2021

Abstract Objectives To investigate the activities of ceftolozane/tazobactam and imipenem/relebactam against Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa isolated from hospitalized patients in Mexico in 2017–2021. Methods MICs were determined by CLSI broth microdilution and interpreted using CLSI M100 breakpoints. β-Lactamase genes were identified in ceftolozane/tazobactam-, imipenem/relebactam-, and/or imipenem-non-susceptible isolates. Results Ceftolozane/tazobactam and imipenem/relebactam inhibited 89% and 99% of E. coli isolates (n = 2337), and 87% and 94% of K. pneumoniae isolates (n = 1127). Sixty-four percent of E. coli and 47% of K. pneumoniae had an ESBL non-carbapenem-resistant Enterobacterales (ESBL non-CRE) phenotype. Eighty-six percent and 91% of ESBL non-CRE E. coli and K. pneumoniae were ceftolozane/tazobactam susceptible, and 99.9% and 99.8% were imipenem/relebactam susceptible. Ceftolozane/tazobactam was the most active agent studied against P. aeruginosa (n = 1068; 83% susceptible), 9–28 percentage points higher than carbapenems and comparator β-lactams excluding imipenem/relebactam (78% susceptible). Ceftolozane/tazobactam remained active against 35%–58%, and imipenem/relebactam against 32%–42%, of P. aeruginosa in meropenem-, piperacillin/tazobactam-, and cefepime-non-susceptible subsets. The majority of isolates of ceftolozane/tazobactam-non-susceptible E. coli carried an ESBL, whereas among ceftolozane/tazobactam-non-susceptible K. pneumoniae and P. aeruginosa, the majority carried carbapenemases. The most prevalent carbapenemase observed among E. coli (estimated at 0.7% of all isolates), K. pneumoniae (4.8%) and P. aeruginosa (10.0%) was an MBL. Almost all imipenem/relebactam-non-susceptible E. coli and K. pneumoniae carried MBL or OXA-48-like carbapenemases, whereas among imipenem/relebactam-non-susceptible P. aeruginosa, 56% carried MBL or GES carbapenemases. Conclusions Ceftolozane/tazobactam and imipenem/relebactam may provide treatment options for patients infected with β-lactam-non-susceptible Gram-negative bacilli, excluding isolates carrying an MBL- or OXA-48-like carbapenemase.