P-1363. Cefiderocol Activity against Clinical Enterobacterales 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 (e.g. ESBLs, KPC, and OXA-type carbapenemases) and metallo-β-lactamases (MBL). FDC and comparator activities were analyzed against Enterobacterales (ENT) carrying MBL genes, as part of the SENTRY Antimicrobial Surveillance Program. Methods 32,052 ENT were collected from 35 sites in the US and 42 sites in the European (EU) regions during 2020–2023. Susceptibility (S) testing used broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for FDC. CLSI (same as the FDA) breakpoints were used for FDC; whereas CLSI were applied for comparators, except for colistin (EUCAST). ENT with MIC ≥2 mg/L (nonS based on CLSI criteria) for imipenem or meropenem were screened for β-lactamase genes. Results Carbapenem-nonS isolates comprised 2.9% (944/32,052) of the population, of which 1.4% (207/15,147) and 4.4% (737/16,905) originated from US and EU sites, respectively. FDC (94.6–96.6%S) had equivalent MIC90 of 4 mg/L against all carbapenem-nonS isolates, and the US and EU subsets, whereas other agents had S ≤86.5% (Table). FDC had MIC50/90 of 2/4 mg/L against isolates carrying MBL genes, including the blaNDM and blaVIM-1 subsets; in contrast, various other agents had off-scale MIC90 values (i.e. >8 mg/L). FDC MIC90 of 8 mg/L were obtained against isolates carrying blaNDM-5. Conclusion FDC showed potent activity against carbapenem-nonS ENT and those subsets of isolates carrying MBL genes. This potent FDC activity is presented against a particular subset of resistant ENT, for which antibiotic treatment options are limited. FDC should be considered as an important option for the treatment of infections caused by these resistant organisms. Disclosures Rodrigo E. Mendes, PhD, GSK: Grant/Research Support