1670. Activity of Ceftolozane/Tazobactam and Comparators Against Clinical MDR and DTR Pseudomonas aeruginosa isolates – SMART United States 2018-2020

Abstract

Abstract Background Antimicrobial resistance of P. aeruginosa to commonly used β-lactams is typically higher in isolates collected from ICU patients and those with hospital-acquired infections. P. aeruginosa with multidrug-resistance (MDR) or difficult-to-treat resistance (DTR) is especially challenging as clinicians have limited treatment options. Ceftolozane/tazobactam was specifically developed to provide enhanced antibacterial activity against P. aeruginosa. We evaluated the activity of ceftolozane/tazobactam (C/T) and comparators against clinical P. aeruginosa isolates by ward type and length of hospital stay at time of specimen collection, including against MDR and DTR isolates. Methods In 2018-2020, 24 clinical labs participated in the global SMART surveillance program in the United States (US) and each collected up to 250 consecutive gram-negative pathogens per year from patients with bloodstream, intraabdominal, lower respiratory tract, and urinary tract infections. MICs were determined using CLSI broth microdilution and interpreted with CLSI breakpoints. Results C/T and amikacin were the only studied agents with activity >95% against all isolates in all strata, with only small differences between the strata (Table). Susceptibility to commonly used β-lactams was 4-8 percentage points lower among isolates collected ≥48 hours post-admission than < 48h and from patients in ICUs compared to non-ICU wards. Correspondingly, the prevalence of MDR and DTR isolates was higher among isolates collected ≥48 hours post-admission (14.6% and 7.3%, respectively) than < 48h (10.5%/6.1%) and those collected from ICU patients (16.1%/7.2%) than non-ICU (10.0%/5.8%). The pattern of lower susceptibility among isolates collected ≥48h post-admission or in ICUs was less clear when the MDR and DTR subsets were analyzed. C/T remained active against ≥72% of MDR and ≥68% of DTR isolates, 7-31 percentage points higher than ceftazidime/avibactam. Conclusion Based on these in vitro data, C/T represents a treatment option for patients with infections caused by MDR and DTR P. aeruginosa, regardless of time to infection or treatment in the ICU. Disclosures Fakhar Siddiqui, MD, MBA, Merck & Co., Inc.: employee|Merck & Co., Inc.: Stocks/Bonds Karri A Bauer, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds.