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

Objectives 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. Methods 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. Results 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). Conclusion 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.