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Background Cefiderocol is a novel siderophore cephalosporin targeted for activity against carbapenem and multidrug-resistant Gram-negative species, including extended-spectrum β-lactamase (ESBL) and carbapenemase-producing strains. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multi-center consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of cefiderocol and meropenem were determined by broth microdilution according to current CLSI guidelines. Cefiderocol was tested in iron-depleted cation-adjusted Mueller–Hinton (MH) broth, meropenem was tested in cation-adjusted MH broth. Cefiderocol MICs were read as the first drug well in which the growth was significantly reduced (i.e., a button of <1 mm or light/faint turbidity) relative to the growth observed in the growth control well containing the same medium. Trailing endpoints were disregarded. Isolates tested included 35 Escherichia coli, five Enterobacter/Citrobacter group, and 794 Klebsiella pneumoniae. Isolates had characterized β-lactamases including TEM, SHV, and CTX-M ESBLs and KPC, NDM, and OXA carbapenemases. Results Cefiderocol MICs ranged from ≤0.03 to >64 mg/L, with overall MIC50 of 0.5 mg/L and MIC90 of 4 mg/L (table). MIC90 value (≤0.03 mg/L) was lowest against isolates with no ESBLs or carbapenemases. MIC90 was 1 mg/L for OXA and TEM/SHV groups, 2–4 mg/L for KPC-3 groups and 8 mg/L for NDM and KPC-2 groups. Conclusion Compared with isolates without ESBLs and carbapenemases, cefiderocol shows higher MICs against isolates with ESBLs, including TEM, SHV, and CTX-M and carbapenemases including KPC, NDM, and OXA. The clinical utility of cefiderocol against ESBL and carbapenemase-producing Enterobacteriaceae is dependent on the pharmacokinetic and pharmacodynamic properties of cefiderocol.Table: Activity of Cefiderocol β-Lactam Resistance N MIC range (mg/L) MIC50 (mg/L) MIC90 (mg/L) ampC 3 0.25 to 2 NA NA KPC-2 255 ≤0.03 to 32 0.5 8 KPC2 + Other 101 ≤0.03 to 16 2 8 KPC-3 276 ≤0.03 to 64 0.25 2 KPC3 + Other 106 ≤0.03 to 16 0.5 4 NDM 28 0.25 to >64 2 8 OXA 8 ≤0.03 to 1 0.25 1 TEM/SHV ESBL 42 ≤0.03 to >64 2 1 None 15 ≤0.03 to 0.12 ≤0.03 ≤0.03 All 834 ≤0.03 to >64 0.5 4 Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, Shionogi: Scientific Advisor, Consulting fee. achaogen: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Consultant, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee.

open forum infectious diseases

1351. In vitro Activity of Cefiderocol (S-649266), a Siderophore Cephalosporin, Against Enterobacteriaceae With Defined Extended-Spectrum Β-Lactamases and Carbapenemases