P-1364. Cefiderocol Activity against <i>Pseudomonas aeruginosa</i> Clinical Isolates Carrying Metallo-β-lactamase Genes in United States and European Hospitals (2020–2023)

Abstract Background Cefiderocol (FDC) is a siderophore cephalosporin that uses the iron transport systems of Gram-negative bacteria to optimize cell entry. FDC is stable to hydrolysis by serine and metallo-β-lactamases (MBL). FDC and comparator activities were analyzed against P. aeruginosa (PSA) carrying MBL genes, as part of the SENTRY Antimicrobial Surveillance Program. Methods 9,573 PSA were collected from 36 sites in the US and 43 sites in Europe (EU) in 2020–2023. Susceptibility (S) testing used broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for FDC. CLSI/EUCAST breakpoints were used for FDC; whereas CLSI were applied for comparators (EUCAST for colistin [COL]). Isolates with MIC ≥4 mg/L (nonS by CLSI) for imipenem or meropenem were screened for β-lactamase genes. Results Carbapenem-nonS PSA comprised 23.4% (2,236/9,573) of isolates, with 22.3% (980/4,400) and 24.3% (1,256/5,173) originating from US and EU sites, respectively (Table). 5.5% (124/2,236) of PSA carried MBL, and these PSA were mostly from EU (94.4%). FDC (98.3–99.4%S) had MIC50 of 0.12 mg/L and MIC90 of 0.5 mg/L against carbapenem-nonS PSA from the US and EU, whereas other agents had lower S (80.9–90.2%), except for COL (99.7–99.8%S). Aztreonam-avibactam inhibited only 48.4% and 57.6% of carbapenem-nonS PSA from the US and EU at MIC of ≤8 mg/L, respectively. FDC (MIC50/90, 0.25/2 mg/L; 94.4–96.0%S) had activity against the MBL-carrying PSA subset; in contrast, other agents had off-scale MIC90 (i.e. &amp;gt;8 mg/L), except for COL (100%S). All PSA carrying blaIMP and blaVIM were susceptible to FDC (MIC90/100, 1/2 mg/L), whereas higher FDC MIC (MIC50/90, 2/16 mg/L; 57.1–64.3%S) were noted against blaNDM-carrying PSA. Conclusion FDC showed potent activity against carbapenem-nonS PSA clinical isolates from US and EU hospitals, including isolates carrying MBL genes, whereas newly launched BL/BLI didn’t show activity. FDC should be considered as an important option for the treatment of infections caused by these resistant subsets for which antibiotic treatment option are limited. Disclosures Rodrigo E. Mendes, PhD, GSK: Grant/Research Support