Antimicrobial activity of ceftolozane/tazobactam, imipenem/relebactam, and comparators against Gram-negative pathogens collected in Arabian Gulf countries: SMART 2020-2024.

To investigate the in vitro susceptibility of recent clinical Enterobacterales and Pseudomonas aeruginosa isolates collected in the Arabian Gulf region to ceftolozane/tazobactam, imipenem/relebactam, and comparator antimicrobial agents. From 2020 to 2024, two clinical laboratories in Kuwait and one each in Qatar, the United Arab Emirates, and Oman (participated in 2022-2024 only) 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 2025 EUCAST breakpoints. Most imipenem, imipenem/relebactam, and ceftolozane/tazobactam non-susceptible isolates were interrogated for their acquired β-lactamase content. Ceftolozane/tazobactam was active against 85.6% of the Enterobacterales (n = 3,603), including 92.0% of ESBL-positive, non-CRE (non-carbapenem-resistant Enterobacterales) phenotype Escherichia coli and 91.6% of ESBL-positive, non-CRE phenotype Klebsiella pneumoniae, but was poorly active against MDR (multiple-drug resistant) isolates (21.6% susceptible). In total, 90.6% of non-Morganellaceae Enterobacterales (n = 3,421) were imipenem/relebactam-susceptible, including 95.6% of the E. coli and 80.7% of the K. pneumoniae. Pseudomonas aeruginosa isolates (n = 1,347) were highly susceptible to both ceftolozane/tazobactam and imipenem/relebactam, with 91.2% and 89.0% inhibited, respectively. Both ceftolozane/tazobactam and imipenem/relebactam retained activity against ≥70% of cefepime-resistant, ceftazidime-resistant, and piperacillin/tazobactam-resistant P. aeruginosa. Ceftolozane/tazobactam inhibited the greatest percentage of meropenem-resistant P. aeruginosa (66.9%) among comparator β-lactam antimicrobials. Molecular characterization showed that the majority of both the imipenem/relebactam- and ceftolozane/tazobactam-resistant Enterobacterales harbored the NDM metallo-β-lactamase (MBL). Most of the imipenem/relebactam-resistant P. aeruginosa characterized did not possess acquired β-lactamases, while the majority of those resistant to ceftolozane/tazobactam carried a variety of acquired enzymes, including MBLs (IMP, VIM, NDM) and ESBLs (VEB, GES). Recent clinical isolates of Enterobacterales collected in the Arabian Gulf region were highly susceptible to imipenem/relebactam, while both imipenem/relebactam and ceftolozane/tazobactam exhibited excellent activity against P. aeruginosa. However, the incidence of MBLs in the region remains a significant concern for future therapeutic strategies.