151. Simplifying Empiric Antimicrobial Therapy Selection for Lower Respiratory Tract Infections in Intensive Care Unit Patients: Using Resistance Frequency to Guide Decision Making

Abstract Background In the US, the burden of multidrug resistant bacterial infections, including carbapenem-resistant P. aeruginosa (CRPA) and ESBL-producing Enterobacterales (ESBL-E), is substantial. These resistant pathogens may affect the delivery of timely effective therapy. The aim of this study is to evaluate beta-lactam (BL) susceptibility trends based on the aggregate frequency of CRPA and a combined ESBL-E phenotype (K. pneumoniae (KPn) + E. coli (EC)) observed in critically ill patients with lower respiratory tract infections (LRTI). Methods In 2016-2019, ~20 US institutions per year submitted up to 250 gram-negative pathogens as part of the Study for Monitoring Antimicrobial Resistance Trends. A total of 871 PA, 380 KPn, and 336 EC isolates were collected from ICU patients with LRTI. MICs were determined using broth microdilution and interpreted using 2021 CLSI breakpoints. ESBL-E phenotype was defined as: ceftriaxone MIC ≥ 2 mcg/mL. Institutions were stratified into two groups based on frequency of CRPA and combined ESBL-E phenotype: Group 1: CRPA ≤ 15% and ESBL-E ≤ 15%; Group 2: CRPA > 15% and ESBL-E > 15%. Based on CLSI guidance, an empiric antibiotic susceptibility threshold of ≥90% was deemed optimal. Results Overall, CRPA and ESBL-E phenotypes were identified in 28.4% and 21.2% of isolates, respectively. Aggregate BL susceptibility in group 1 was above the 90% threshold for cefepime (FEP), piperacillin/tazobactam (TZP), meropenem (MEM), ceftolozane/tazobactam (C/T), and imipenem/relebactam (I/R) (Table 1). However, as frequency of CRPA and ESBL-E exceeded 15%, aggregate BL susceptibility declined to 77.3%, 79.3%, and 86.2% for FEP, TZP, and MEM, respectively. In contrast, C/T and I/R maintain susceptibility above the empiric susceptibility threshold. Table 1. Aggregate susceptibility of P. aeruginosa, E. coli, and K. pneumoniae ICU LRTI isolates stratified by resistance frequency: Best- (Group 1) and worst-case (Group 2) scenarios Conclusion In ICU patients, exceeding CRPA and combined ESBL-E phenotype frequency of 15% for both classifications, impacts susceptibility to 1st line BL’s resulting in a failure to achieve empiric susceptibility thresholds. This stratification could serve as a decision point for triggering earlier susceptibility testing or modifying empiric therapy recommendations for LRTI to include newer agents pending microbiology results. Disclosures Kenneth Klinker, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co., Inc. (Employee, Shareholder) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Karri A. Bauer, PharmD, Merck & Co., Inc. (Employee, Shareholder)