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Background Ceftolozane-tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. The combination was cleared by FDA and EMA and is approved in the United States and over 60 countries worldwide. Relebactam (REL) is an inhibitor of class A and C β-lactamases that is in clinical development in combination with imipenem (IMI). Using clinical isolates collected in the United States as part of the global SMART surveillance program, we compared the activity of C/T and IMI/REL against P. aeruginosa (PA) isolates. Methods In 2016–2018, 29 clinical laboratories from the United States collected up to 250 consecutive, aerobic or facultatively anaerobic, gram-negative pathogens (GNP) from blood, intra-abdominal, urinary, and lower respiratory tract infections. A total of 14,606 GNP were collected, of which 2,774 were PA. MICs were determined using CLSI broth microdilution and interpreted with CLSI 2019 breakpoints; IMI breakpoints were used for IMI/REL. Results The activity of C/T and IMI/REL against 2,774 PA is shown (table). Among all PA, 1.8% of isolates were nonsusceptible (NS) to both agents; 4.4% were susceptible (S) to C/T but not to IMI/REL, and 2.9% were susceptible to IMI/REL but not to C/T. Among the subset of isolates collected from patients in ICUs (n = 827), 87.3% were susceptible to both C/T and IMI/REL, 2.7% were nonsusceptible to both agents, 5.8% of isolates were susceptible only to C/T, and 4.2% of isolates were susceptible only to IMI/REL. Among all C/T-NS isolates (all patient locations, n = 132), 61.4% were IMI/REL-S and &lt;30% were susceptible to all other studied β-lactams and fluoroquinolones. Among all IMI/REL-NS isolates (n = 173), 70.5% were C/T-S and &lt;36% were susceptible to all other studied β-lactams and fluoroquinolones. Of the tested agents, only amikacin and colistin exceeded the activity of C/T or IMI/REL against these NS subsets. Conclusion Resistance to C/T or IMI/REL was not common among recent clinical isolates of PA collected in the United States, and both agents promise to be important treatment options. A significant proportion of isolates nonsusceptible to one agent was susceptible to the other, especially among isolates from patients in ICUs. The data suggest that susceptibility to both agents should be tested at hospitals. Disclosures All authors: No reported disclosures.

597. Cross-resistance of Ceftolozane-Tazobactam and Imipenem-Relebactam Against Clinical P. aeruginosa Isolates: SMART United States 2016–2018