642. <i>In Vitro</i> Activity of Cefiderocol and Comparator Agents Against Molecularly Characterized Enterobacterales Clinical Isolates Causing Infection in United States Hospitals (2020-2021)

Abstract Background Cefiderocol (CFDC) is a siderophore cephalosporin that hijacks the Gram-negative bacteria iron transport system to facilitate cell entry and reach its target. CFDC remains stable hydrolysis in presence of serine β-lactamases (ESBLs, KPC, OXA-type carbapenemases) metallo-β-lactamases (MBL). comparator activities were analyzed against Enterobacterales (ENT), including molecularly characterized isolates, as part SENTRY Antimicrobial Surveillance Program USA. Methods 8,328 ENT collected from 32 sites 2020-2021. Susceptibility testing was performed by broth microdilution. used iron-depleted media. CLSI breakpoints used. E. coli, K. pneumoniae, P. mirabilis with ceftriaxone, ceftazidime, or aztreonam MIC ≥2 μg/mL, any displaying μg/mL for imipenem (excluded mirabilis, penneri, indole-positive Proteeae) meropenem (MER), subjected genome sequencing screening β-lactamase genes. Results In general, (≥ 99.9% susceptible [S]), imipenem-relebactam (IMR; 99.4-100%S), meropenem-vaborbactam (MEV; 100%S), ceftazidime-avibactam (CZA; 100%S) active carbapenem-susceptible carried ESBL and/or AmpC genes (Table). (MIC50/90, 0.5/4 μg/mL; 98.4%S) CZA 1/8 91.2%S) most agents carbapenem-nonS whereas IMR 0.25/4 81.6%S) MEV 0.12/8 86.4%S) had suboptimal activity. 0.5/2 μg/mL), 0.12/0.5 0.03/0.5 1/2 μg/mL) (100%S) KPC subset. (MIC, 0.5-4 also carrying MBL genes, 0.5-2 (1-4 isolates blaOXA-48-like. Conclusion activity consistent, regardless phenotypes genotypes, carbapenemase other than blaKPC, where approved β-lactam/β-lactamase inhibitor combinations showed limited These data reinforce an important option treatment infections caused resistant subsets. Disclosures Rodrigo Mendes, PhD, AbbVie: Grant/Research Support|Cidara: Support|GSK: Support|Melinta: Support|Nabriva Therapeutics: Support|Office Assistant Secretary Defense Health Affairs: Support|Pfizer: Support|Shionogi: Support|Spero Support John H. Kimbrough, Valerie Kantro, BA, Dee Shortridge, Support|JMI Laboratory: Employee|Melinta: Support|Menarini: Helio S. Sader, MD, Jennifer M. Streit, BS, MT(ASCP), Cidara: Mariana Castanheira, Support.