Cell experiment:

For the determination of cefiderocol MIC, iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) is prepared, except for the cases that are required to determine MICs under specific conditions. The quality control MIC ranges of cefiderocol are 0.06 to 0.5 μg/mL for both E. coli ATCC 25922 and P. aeruginosa ATCC 27853. For anaerobic bacteria, brucella agar supplemented with hemin, vitamin K1, and laked sheep blood is used. For recombinant strains, test medium is supplemented with 10 μg/mL of gentamicin and/or 0.1 mM IPTG (isopropyl-β-d-thiogalactopyranoside) when required[1].

Cefiderocol is a novel siderophore cephalosporin which has a potent activity against a broad range of aerobic Gram-negative bacterial species with MIC50s of 2 μg/mL or less.

Cefiderocol (CFDC; S-649266), a novel parenteral siderophore cephalosporin conjugated with a catechol moiety, has a characteristic antibacterial spectrum with a potent activity against a broad range of aerobic Gram-negative bacterial species, including carbapenem-resistant strains of Enterobacteriaceae and nonfermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP3) of Enterobacteriaceae and nonfermenting bacteria similar to that of ceftazidime. A deficiency of the iron transporter PiuA in P. aeruginosa or both CirA and Fiu in Escherichia coli can cause 16-fold increases in cefiderocol MICs, suggesting that these iron transporters contribute to the permeation of cefiderocol across the outer membrane. The deficiency of OmpK35/36 in Klebsiella pneumoniae and the overproduction of efflux pump MexA-MexB-OprM in P. aeruginosa show no significant impact on the activity of cefiderocol[1].

[1]. Ito A, et al. In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1).