P-1155. Activity of Ceftolozane/Tazobactam, Imipenem/Relebactam and Comparators Against non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa Isolated from Patients with Invasive Respiratory Infections: SMART United States, 2021-2023

Abstract Background Gram-negative bacteria can be the cause of life-threating invasive respiratory tract infections (RTIs), including pneumonia, tracheobronchitis, and lung abscesses. Imipenem/relebactam (IMR) is a combination of imipenem with the β-lactamase inhibitor relebactam. Ceftolozane/tazobactam (C/T) combines ceftolozane, an anti-pseudomonal cephalosporin, with tazobactam. We evaluated the activity of IMR, C/T and comparators against isolates of non-Morganellaceae Enterobacterales (NME) and Pseudomonas aeruginosa (PA) that were collected in the US for the SMART surveillance program (2021-2023) from patients with invasive and non-invasive respiratory samples stratified by length of hospital stay (< 48h [presumed community-acquired infections] vs. ≥48h [presumed hospital-acquired infections]). Methods In 2021-2023, 27 sites in the US collected up to 100 Gram-negative pathogens per year from patients with RTIs. Invasive vs. non-invasive disease categories were based on sampling source (invasive: bronchial brushing, bronchoalveolar lavage, endotracheal aspirate, lungs, thoracentesis; non-invasive: sputum or other). MICs were determined via CLSI broth microdilution and interpreted with 2025 CLSI criteria. Among Enterobacterales, only NME were considered as the Morganellaceae display intrinsic reduced susceptibility to imipenem by a mechanism other than β-lactamase production. Results Susceptibility to commonly used β-lactams was generally lower among NME from presumed hospital-acquired infections compared to community-acquired (Fig. 1). No clear pattern was linked to invasive vs. non-invasive infections. IMR and meropenem were the most active agents in all categories, inhibiting >97% of the NME. Among PA, isolates from invasive samples consistently displayed lower susceptibility than those from non-invasive infections, regardless of length of hospital stay (Fig. 2). C/T was the most active agent in all categories (inhibiting ≥94.7%) followed by IMR (≥87.4% inhibited). Conclusion IMR is an important treatment option for patients with respiratory tract infections caused by NME, while C/T was the most active agent against P. aeruginosa causing RTIs, regardless of length of stay or invasive disease. Disclosures Mark G Wise, PhD, IHMA: Employee Karri A. A. Bauer, PharmD, Merck: Employee Fakhar Siddiqui, MD, MBA, Merck & Co Inc.: Stocks/Bonds (Public Company) Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds (Public Company) Mary Motyl, Ph.D., Merck and Co., Inc.: employee