Susceptibility of Gram-negative pathogens collected in Israel to ceftolozane/tazobactam, imipenem/relebactam and comparators: SMART 2018-22

Mark G Wise; C Andrew DeRyke; Irina Alekseeva; Fakhar Siddiqui; Katherine Young; Mary R Motyl; Daniel F Sahm

doi:10.1093/jacamr/dlae150

Susceptibility of Gram-negative pathogens collected in Israel to ceftolozane/tazobactam, imipenem/relebactam and comparators: SMART 2018-22

JAC Antimicrob Resist. 2024 Sep 17;6(5):dlae150. doi: 10.1093/jacamr/dlae150. eCollection 2024 Oct.

Authors

Mark G Wise¹, C Andrew DeRyke¹, Irina Alekseeva², Fakhar Siddiqui³, Katherine Young³, Mary R Motyl³, Daniel F Sahm¹

Affiliations

¹ IHMA, Schaumburg, IL, USA.
² MSD, Dubai, United Arab Emirates.
³ Merck & Co., Inc., Rahway, NJ, USA.

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: Recent clinical isolates of Enterobacterales and P. aeruginosa collected in Israel were highly susceptible to ceftolozane/tazobactam and imipenem/relebactam.