To assess the in vitro antimicrobial activity of ceftolozane/tazobactam, imipenem/relebactam and comparator agents against clinical isolates of Gram-negative bacilli collected in Israel from 2018 to 2022. Six clinical laboratories each collected up to 250 consecutive Gram-negative isolates per year from patients with bloodstream, intra-abdominal, lower respiratory tract and urinary tract infections. MICs were determined by CLSI broth microdilution and interpreted with 2024 EUCAST breakpoints. Acquired β-lactamase gene carriage was investigated for most ceftolozane/tazobactam- and imipenem/relebactam-resistant isolates. Among the full collection of Enterobacterales (n = 4420), 95.1% were susceptible to ceftolozane/tazobactam, including 95.3% of putative AmpC/ESBL-positive, non-carbapenem-resistant Enterobacterales (CRE) phenotype Escherichia coli and 86.6% of AmpC/ESBL-positive, non-CRE phenotype Klebsiella pneumoniae. Overall, 99.8% of non-Morganellaceae Enterobacterales (n = 3723) were imipenem/relebactam susceptible including 98% of the MDR isolates. Most Pseudomonas aeruginosa isolates (n = 1182) were inhibited by ceftolozane/tazobactam (93.9% susceptible) and imipenem/relebactam (94.7%). Imipenem/relebactam retained activity against ≥78% of cefepime-resistant, ceftazidime-resistant, and piperacillin/tazobactam-resistant P. aeruginosa, while ceftolozane/tazobactam inhibited the greatest percentage of meropenem-resistant P. aeruginosa (67.4%) among comparator β-lactam antimicrobials. Molecular characterization showed the majority of imipenem/relebactam-resistant Enterobacterales harboured a metallo-β-lactamase, while half of the ceftolozane/tazobactam-resistant Enterobacterales carried an acquired ESBL or AmpC. Most of the imipenem/relebactam- and ceftolozane/tazobactam-resistant P. aeruginosa characterized did not possess acquired β-lactamases. Recent clinical isolates of Enterobacterales and P. aeruginosa collected in Israel were highly susceptible to ceftolozane/tazobactam and imipenem/relebactam.

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