Long–term trends in ceftolozane–tazobactam susceptibility among gram–negative pathogens in the United States: a nine–year SMART analysis (2016–2024)

Abstract Objectives To evaluate trends in the susceptibility of clinical Enterobacterales and Pseudomonas aeruginosa from the USA to ceftolozane/tazobactam. Methods The SMART surveillance programme collected 30 658 Enterobacterales and 7454 P. aeruginosa isolates from 37 unique clinical sites in the USA from 2016 to 2024. Nine sites contributed isolates each year. MICs were determined by broth microdilution testing and interpreted using 2025 CLSI breakpoints. Ceftolozane/tazobactam nonsusceptible Enterobacterales were examined for β-lactamase carriage. Results Overall, 93.9% and 95.8% of clinical isolates of Enterobacterales and P. aeruginosa were susceptible to ceftolozane/tazobactam, respectively. Considering all participating sites, annual percent susceptible values for ceftolozane/tazobactam against Enterobacterales ranged from 95.3% (2018, n = 3657) to 92.0% (2024, n = 3249) with a statistically significant decreasing trend (P < 0.001; Cochran-Armitage test). Limiting analysis solely to the nine clinical sites that participated in each year confirmed this trend [range: 94.5% susceptible (2019, n = 1609) to 91.4% susceptible (2024, n = 1544); P = 0.007]. Including all sites, P. aeruginosa percent susceptible values for ceftolozane/tazobactam remained consistent from 2016 (95.0%) to 2024 (95.0%) [range: 94.5% (2017, n = 991) to 96.9% (2020, n = 817)]. However, considering solely the consistently contributing sites, the rate of ceftolozane/tazobactam susceptibility increased [P = 0.013; range: 91.9% (2017, n = 371) to 96.4% (2024, n = 391)]. The incidence of NDM metallo-β-lactamase and CTX-M ESBLs among ceftolozane/tazobactam nonsusceptible Enterobacterales each exhibited a statistically significant increasing trend. Conclusions From 2016 to 2024, ceftolozane/tazobactam activity against US P. aeruginosa remained consistently high; however, a trend of marginally decreasing susceptibility to ceftolozane/tazobactam among Enterobacterales was observed, likely associated with increased incidence of NDM- and CTX-M-producers.