ARGONAUT-I: Activity of Cefiderocol (S-649266), a Siderophore Cephalosporin, against Gram-Negative Bacteria, Including Carbapenem-Resistant Nonfermenters and Enterobacteriaceae with Defined Extended-Spectrum β-Lactamases and Carbapenemases

Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01801-18. doi: 10.1128/AAC.01801-18. Print 2019 Jan.

Abstract

The activity of the siderophore cephalosporin cefiderocol is targeted against carbapenem-resistant Gram-negative bacteria. In this study, the activity of cefiderocol against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae strains was determined by microdilution in iron-depleted Mueller-Hinton broth. The MIC90s against A. baumannii, S. maltophilia, and P. aeruginosa were 1, 0.25, and 0.5 mg/liter, respectively. Against Enterobacteriaceae, the MIC90 was 1 mg/liter for the group harboring OXA-48-like, 2 mg/liter for the group harboring KPC-3, and 8 mg/liter for the group harboring TEM/SHV ESBL, NDM, and KPC-2.

Keywords: Enterobacteriaceae; Gram-negative bacteria; S-649266; cefiderocol; cephalosporin; siderophore.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / enzymology
  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / growth & development
  • Anti-Bacterial Agents / pharmacology*
  • Cephalosporins / pharmacology*
  • Culture Media
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / growth & development
  • Gene Expression
  • Gram-Negative Bacterial Infections / drug therapy
  • Gram-Negative Bacterial Infections / microbiology
  • Humans
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / genetics
  • Pseudomonas aeruginosa / growth & development
  • Siderophores / pharmacology
  • Stenotrophomonas maltophilia / drug effects*
  • Stenotrophomonas maltophilia / enzymology
  • Stenotrophomonas maltophilia / genetics
  • Stenotrophomonas maltophilia / growth & development
  • beta-Lactam Resistance / drug effects
  • beta-Lactam Resistance / genetics
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Culture Media
  • Siderophores
  • cefiderocol
  • beta-Lactamases