P-1100. Activity of Cefiderocol and Comparator Agents Against Global Isolates of Stenotrophomonas maltophilia from the SENTRY Antimicrobial Surveillance Program (2020–2023)
Authors: Onishi Motoyasu , Yamashiro Hidenori , Maher Joshua , Kimbrough Hank , Mendes Rodrigo E , DeJonge Boudewijn L , Nguyen Sean T , Longshaw Christopher M , Takemura Miki , Yamano Yoshinori 
Published: January 2025

Abstract

Background
Stenotrophomonas maltophilia is a ubiquitous multidrug-resistant opportunistic pathogen. Infections caused by S. maltophilia have limited antibiotics treatment options due to the intrinsic resistant mechanisms such as the production of chromosomal L1 metallo-type carbapenemase and L2 extended-spectrum type β-lactamase. Cefiderocol (FDC) is a siderophore-conjugated cephalosporin with broad activity against Gram-negative bacteria, including S. maltophilia. In this study, the in vitro activities of cefiderocol and comparators were investigated against S. maltophilia clinical isolates that were collected from the US and Europe in 2020-2023 as part of the SENTRY Antimicrobial Surveillance Program.
Susceptibility of Stenotrophomonas maltophilia to cefiderocol and comparator agents
Cefiderocol (FDC), levofloxacin (LVFX), trimethoprim-sulfamethoxazole (TMP-SMX), minocycline (MIN), ceftazidime (CAZ), imipenem-relebactam (I/R), ceftazidime-avibactam (CZA), non-susceptible (NS), susceptible (S), intermediate (I), resistant (R), N/A (not applicable), a cefiderocol S ≤1, levofloxacin S ≤2, trimethoprim-sulfamethoxazole S ≤2/38, minocycline S ≤1, breakpoints as published by CLSI (2024), b cefiderocol S ≤2, levofloxacin S ≤0.5, ceftazidime S≤4, imipenem-relebactam S ≤2, ceftazidime-avibactam S ≤8, PK-PD breakpoints as published by EUCAST (2023)

Methods
A total of 1782 S. maltophilia isolates were consecutively collected from the US and Europe from 2020-2023. The most common infection type from which isolates were collected was pneumonia (n=1193), followed by skin and skin structure (n=166), bloodstream infection (n=208), and urinary tract infections (n=56). Minimum inhibitory concentrations (MICs) of FDC and comparators were determined by using iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) for cefiderocol and CAMHB for comparators. MIC50, MIC90, and MIC range were calculated. Susceptibility rates were determined by using CLSI breakpoints (2024) and EUCAST PK-PD breakpoints (2023).

Results
FDC was the most potent agent tested against S. maltophilia, showing the lowest MIC90 value of 0.25 µg/mL (Table). The MIC90 values of levofloxacin (LVFX), trimethoprim-sulfamethoxazole (TMP-SMX), and minocycline (MIN) were 4, 0.5, and 1 µg/mL, respectively. The MIC90 values of other comparator agents were &gt;8 µg/mL. Susceptibilities of FDC, LVFX, SMT, and MIN were 99.3, 83.0, 97.0, and 93,0%, respectively. The susceptibility to FDC was the highest against LVFX-, TMP-SMX- or MIN-non-susceptible isolates according to both CLSI and EUCAST breakpoint (Table).

Conclusion
FDC showed potent in vitro activity against S. maltophilia collected in the US and Europe from 2020-2023, including isolates non-susceptible to LVFX, TMP-SMX, or MIN, suggesting that FDC is an important therapeutic option for S. maltophilia infections.

Disclosures
Motoyasu Onishi, PhD, Shionogi & Co., Ltd.: Employee Hidenori Yamashiro, Shionogi & Co., Ltd.: Employee Rodrigo E. Mendes, PhD, GSK: Grant/Research Support Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Sean T. Nguyen, PharmD, Shionogi Inc.: Employee Christopher M. Longshaw, PhD, Shionogi BV: Employee Miki Takemura, n/a, Shionogi & Co., Ltd.: Employee Yoshinori Yamano, PhD, Shionogi & Co., Ltd.: Employee