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. [Figure: see text] 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 MIC(50) of 0.12 mg/L and MIC(90) 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 (MIC(50/90), 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 MIC(90) (i.e. >8 mg/L), except for COL (100%S). All PSA carrying bla(IMP) and bla(VIM) were susceptible to FDC (MIC(90/100), 1/2 mg/L), whereas higher FDC MIC (MIC(50/90), 2/16 mg/L; 57.1–64.3%S) were noted against bla(NDM)-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