P-1264. The Long View: Tracking Gram-negative Susceptibility Trends from 2010-2024 to Inform Stewardship

Abstract Background The rise in antimicrobial resistance (AMR) among Gram-negative bacteria poses significant treatment challenges. This study evaluated susceptibility trends over a 15-year period for key Gram-negative organisms at UK HealthCare (UKHC) to guide stewardship strategies and empirical therapy. Methods A retrospective review of cumulative antimicrobial susceptibility data from 2010 to 2024 was conducted for K. aerogenes, E. coli, K. pneumoniae, P. aeruginosa, S. marcescens, and E. cloacae. Susceptibility to cefepime, piperacillin-tazobactam, levofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole (TMP-SMX), and meropenem were analyzed. Trend lines were generated using linear regression to assess changes over time. Results Over the 15-year period, notable declines in susceptibility were observed among Enterobacterales, particularly K. pneumoniae and E. coli. Cefepime susceptibility declined from 98% to 81% (R² = 0.8291) in K. pneumoniae and from 95% to 83% (R² = 0.7809) in E. coli. For K. pneumoniae, susceptibilities fell for piperacillin-tazobactam (90% to 74%, R² = 0.5163), ceftriaxone (91% to 81%, R² = 0.7448) and TMP-SMX (95% to 80%, R² = 0.6504). E. coli also showed declining susceptibility to ceftriaxone (R² = 0.4627) and cefepime (R² = 0.7809) though piperacillin-tazobactam susceptibility remained stable above 90%. K. aerogenes exhibited declines across all agents, particularly levofloxacin and cefepime. In contrast, P. aeruginosa demonstrated stable or slightly improving susceptibility to cefepime, meropenem, and piperacillin-tazobactam. S. marcescens showed minimal variability in susceptibility, while E. cloacae experienced modest declines, especially to ceftriaxone and piperacillin-tazobactam. Conclusion At UKHC, antimicrobial resistance among Enterobacterales, especially K. pneumoniae and E. coli, continues to worsen, driven by declining susceptibility to key beta-lactams and fluoroquinolones. Meanwhile, susceptibility among P. aeruginosa and S. marcescens has remained relatively stable. These findings highlight the critical need for robust antimicrobial stewardship interventions and local, data-driven empiric prescribing, supported by ongoing surveillance and rapid diagnostics. Disclosures All Authors: No reported disclosures