1674. Trends in Antimicrobial Susceptibility to Ceftolozane/Tazobactam and Comparators of Pseudomonas aeruginosa from Patients with Respiratory Tract Infections in Five Latin American Countries – SMART 2017-2020

Abstract

Abstract Background Ceftolozane is a cephalosporin specifically developed to have enhanced antibacterial activity against P. aeruginosa. Combined with tazobactam, it was approved by FDA and EMA for hospital-acquired/ventilator-associated bacterial pneumonia. We evaluated trends in the activity of ceftolozane/tazobactam (C/T) against P. aeruginosa isolates collected as part of the global SMART surveillance program from patients with lower respiratory tract infections (RTI) in Argentina, Brazil, Chile, Colombia, and Mexico. Methods In 2017-2020, 29 clinical labs each collected up to 100 consecutive gram-negative pathogens per year from patients with RTI. A total of 6,036 isolates were collected < 48 or ≥48 hours post-admission, of which 1,679 (27.8%) were P. aeruginosa. MICs were determined using CLSI broth microdilution and breakpoints. C/T- or imipenem-nonsusceptible isolates were screened for genes encoding β-lactamases. Results Using only isolates from the 21 sites that participated in all 4 years, variability in susceptibility was seen over the study period among isolates collected < 48h post-admission, with a significant increasing trend in susceptibility only for C/T, while susceptibility was lower and more stable among isolates collected ≥48h (Figure). These patterns correlated with estimated carbapenemase rates, especially among isolates collected < 48h post-admission (9.7%, 4.2%, 8.1%, 1.6% carbapenemase-positive per year 2017-2020). Using isolates from all sites from the two most recent years to assess country-level susceptibility, substantial variability was seen. For example, susceptibility to C/T of isolates collected after 48h ranged from 62.5% for Chile (n=120) to ≥92% for Argentina (n=128) and Brazil (n=183), 12-31 percentage points higher than meropenem and piperacillin/tazobactam. This geographic pattern correlated with estimated carbapenemase rates (36% of isolates collected in Chile 48h post-admission versus ≤4% for Argentina and Brazil). Conclusion Variability in antimicrobial susceptibility of P. aeruginosa from RTI was seen across Latin American countries, but overall no significant decreases in susceptibility were found over the study period. C/T remained the most active among the studied agents. Disclosures Fakhar Siddiqui, MD, MBA, Merck & Co., Inc.: employee|Merck & Co., Inc.: Stocks/Bonds Jacqueline Pavia, MD, MSD COLOMBIA: EMPLOYEE Charles A. DeRyke, PharmD, Merck & Co., Inc. Merck Research Laboratories: Stocks/Bonds Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds.