P-1484. <i>In vitro</i> Activity of Cefiderocol and Comparator Agents Against Non-fermentative Gram-negative Bacilli Isolated from Patients Hospitalized with Pneumonia as part of the SENTRY Global Surveillance Program (2020-2022)

Abstract Background Cefiderocol (CFDC) is a siderophore-conjugated cephalosporin with broad activity against Gram-negative bacteria including non-fermenters resistant to carbapenems. The in vitro activity of CFDC and comparators was evaluated against glucose non-fermenting Gram-negative bacteria isolated from patients hospitalized with pneumonia.Table 1:Activity of cefiderocol and comparator agents against Pseudomonas aeruginosa, Acinetobacter baumannii-calcoaceticus complex, and Stenotrophomonas maltophilia isolates from patients hospitalized with pneumonia from 2020-2022 Methods 5,995 isolates were collected between 2020-2022 from pneumonia patients as part of the global SENTRY Antimicrobial Surveillance Program, including: 3,809 Pseudomonas aeruginosa (PSA), 1,092 Acinetobacter baumannii-calcoaceticus complex (ABC), 808 Stenotrophomonas maltophilia (STM), 104 Achromobacter spp. (ACHR), 81 Burkholderia cepacia complex (BURK), and 101 other isolates. Minimum inhibitory concentrations (MIC) were assessed by CLSI guidelines using broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for CFDC. Susceptibility was assessed according to 2024 CLSI, FDA, and EUCAST breakpoints. Carbapenem resistance (CR) was defined as resistant to meropenem and imipenem by CLSI breakpoints. Results Against PSA, CFDC and β-lactam/β-lactamase inhibitor combinations all had susceptibility &amp;gt;95%. However only CFDC maintained high susceptibility against CR-PSA with 99.3% of the isolates being susceptible by CLSI breakpoints. No other comparator had &amp;gt; 90% susceptibility against CR-PSA (Table 1). Against ABC, CFDC demonstrated 97.5% susceptibility by CLSI breakpoints. This high susceptibility was maintained against CR-ABC with 96.1% susceptibility using CLSI breakpoints. Colistin showed 75.5% susceptibility per EUCAST breakpoint, but ceftazidime and ampicillin-sulbactam had no appreciable activity. CFDC, trimethoprim-sulfamethoxazole, and minocycline all showed &amp;gt;90% susceptibility against STM. Against ACHR and BURK, CFDC had high activity, with MIC50/90 values of 0.03/0.5 and 0.06/1 mg/L, respectively. Conclusion CFDC demonstrated high in vitro activity against glucose non-fermenters isolated from hospitalized patients with pneumonia. In particular, CFDC maintained high susceptibility against CR isolates making it an important treatment option for pneumonia patients at risk of infection with a CR non-fermenter. Disclosures Frank Kung, PhD, Shionogi Inc: Employee Sean T. Nguyen, PharmD, Shionogi Inc.: Employee Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Christopher M. Longshaw, PhD, Shionogi BV: Employee Jason J. Bryowsky, PharmD, MS, Shionogi: Employee Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Miki Takemura, n/a, Shionogi &amp; Co., Ltd.: Employee Yoshinori Yamano, PhD, Shionogi &amp; Co., Ltd.: Employee