P-1514. Cefepime-taniborbactam Exhibits Limited Cross-resistance with Ceftazidime-avibactam and Ceftolozane-tazobactam against Carbapenem-nonsusceptible Enterobacterales and Multidrug-resistant <i>Pseudomonas aeruginosa</i> from the United States 201

Abstract Background Cefepime-taniborbactam (FTB) is an investigational β-lactam/β-lactamase inhibitor combination with activity against most isolates of carbapenem-resistant and multidrug-resistant (MDR) Enterobacterales and P. aeruginosa. We evaluated the activity of FTB and comparators against clinical isolates of Enterobacterales and P. aeruginosa from the US and assessed FTB cross-resistance to ceftazidime-avibactam (CZA) and ceftolozane-tazobactam (CT) in resistant subsets. Methods MICs were determined by CLSI reference broth microdilution against Enterobacterales (n=4,932) and P. aeruginosa (n=1,508) collected in the US in 2018-2022. Phenotypes were based on 2024 CLSI breakpoints. A provisional FTB susceptible breakpoint of ≤16 µg/mL was used for comparative purposes. An MDR phenotype was defined as resistance to ≥1 agent from ≥3 drug classes. Results Among Enterobacterales, 1.8% of isolates were nonsusceptible to meropenem (MEM; Table 1). FTB was the most active agent, inhibiting 96.7% of MEM-nonsusceptible Enterobacterales isolates at ≤16 µg/mL whereas 80.4% were susceptible to CZA and 87.0% were susceptible to meropenem-vaborbactam (MEV). Among P. aeruginosa, 11.9% of isolates were MDR (Table 1). FTB was the most active agent, inhibiting 82.2% of MDR P. aeruginosa isolates at ≤16 µg/mL whereas 56.1% were susceptible to CT and 63.9% were susceptible to CZA (Table 1). Among MEM-nonsusceptible Enterobacterales, 80.2% were susceptible to both FTB and CZA, 16.5% were susceptible to FTB but not to CZA, 1.1% were susceptible to CZA but not to FTB, and 2.2% were nonsusceptible to both agents (Table 2A). Among MDR P. aeruginosa, 54.4% were susceptible to both FTB and CT, 27.8% were susceptible to FTB but not to CT, 1.7% were susceptible to CT but not to FTB, and 16.1% were nonsusceptible to both agents (Table 2B). Conclusion FTB was active in vitro against recent clinical isolates of Enterobacterales and P. aeruginosa from the US including most isolates resistant to CZA and CT in key resistant subsets. These data support continued development of FTB as a potential treatment option for patients with challenging infections due to carbapenem-resistant Enterobacterales and MDR P. aeruginosa. Disclosures Greg Moeck, PhD, Biomedical Advanced Research and Development Authority (BARDA): Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Grant/Research Support|Venatorx Pharmaceuticals, Inc.: Stocks/Bonds (Private Company) Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant