P-1310. Cefiderocol Remains Active against US Clinical Isolates of Stenotrophomonas maltophilia Non-susceptible to Comparator Agents: Results from the SENTRY Antimicrobial Surveillance Program (2020–2024)

Abstract Background Stenotrophomonas maltophilia is a non-fermenting, multidrug-resistant opportunistic pathogen with limited treatment options due to intrinsic resistance mechanisms, such as the production of the chromosomally encoded metallo-β-lactamase, L1, and the extended-spectrum β-lactamase, L2. The Infectious Disease Society of America listed cefiderocol (FDC), a siderophore conjugated cephalosporin with broad activity against Gram-negative bacteria, as a preferred agent in combination therapy for S. maltophilia infections. In this analysis, the in vitro activities of FDC and comparators, were evaluated against S. maltophilia clinical isolates, including non-susceptible (NS) subsets, collected in the US from 2020-2024 as part of the SENTRY Antimicrobial Surveillance Program.Table.In Vitro Activity of Cefiderocol and Comparator Agents against US Isolates of Stenotrophomonas maltophilia (2020-2024) Methods A total of 1,291 S. maltophilia isolates were consecutively collected from US patients between 2020-2024. Minimum inhibitory concentrations (MICs) were determined by using iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) for FDC and CAMHB for comparators. MIC50, MIC90, and MIC ranges were calculated. Susceptibility was determined using CLSI/FDA breakpoints (2025; MIC ≤1 mg/L). Results The most common infection types from which isolates were collected included pneumonia (n=943; 73.0%), skin/soft tissue (n=112; 8.7%), and blood stream infection (n=100; 7.7%). FDC was the most potent agent tested, with an MIC50/90 value of 0.06/0.25 mg/L, and 99.1% of the isolates being susceptible. MIC50/90 of aztreonam-avibactam was 2/4 mg/L (no interpretive breakpoint established). Susceptibilities to trimethoprim-sulfamethoxazole (SXT), levofloxacin (LVX), and minocycline (MIN) were 97.7%, 81.8%, and 92.1%, respectively. FDC maintained high susceptibility (≥96.7%) against isolates that were NS to LVX, SXT, or MIN and all of isolates NS to LVX, SXT, and MIN remained susceptible to FDC(Table). Conclusion FDC showed potent in vitro activity against S. maltophilia collected in the US from 2020-2024, including against isolates NS to comparator antibiotics, suggesting that FDC is an important therapeutic option for infections caused by S. maltophilia. Disclosures Frank Kung, PhD, Shionogi Inc: Employee Sean T. Nguyen, PharmD, Shionogi Inc: Employee Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Hidenori Yamashiro, Shionogi HQ: Employee Yoshinori Yamano, PhD, Shionogi HQ: Employee