Cefiderocol is a new type of iron carrier cephalosporin with strong in vitro activity against Gram-negative bacteria and non-fermented Gram-negative bacteria[1-3].
Cefiderocol(10/40/70 mg/L;3 days) dampens LPS-stimulated production of pro-inflammatory cytokines[4]. The absence of iron transporters PiuA in Pseudomonas aeruginosa or CirA and Fiu in Escherichia coli resulted in a 16-fold increase in cefiderocol MIC, suggesting that these iron transporters contribute to cefiderocol penetration through the outer membrane[5].
Administering cefiderocol 2 g every 8 h as a 3-h infusion for 4 days achieved a greater than 3 log10 reduction in cells of carbapenem-resistant isolates of P. aeruginosa, A. baumannii, and K. pneumoniae in rat lung infection[6]. The pharmacodynamics of cefiderocol in the thigh infection model of neutropenia mice showed a sigmoid dose-response curve, and the bactericidal effect was better with the increase of dose[7].
References:
[1]. Choi JJ, McCarthy MW. Cefiderocol: a novel siderophore cephalosporin. Expert Opin Investig Drugs. 2018 Feb;27(2):193-197. doi: 10.1080/13543784.2018.1426745. Epub 2018 Jan 24. PMID: 29318906.
[2]. Soriano MC, Montufar J,et,al. Cefiderocol. Rev Esp Quimioter. 2022 Apr;35 Suppl 1(Suppl 1):31-34. doi: 10.37201/req/s01.07.2022. Epub 2022 Apr 22. PMID: 35488822; PMCID: PMC9106201.
[3]. GijÓn Cordero D, Castillo-Polo JA, et,al. Antibacterial spectrum of cefiderocol. Rev Esp Quimioter. 2022 Sep;35 Suppl 2(Suppl 2):20-27. doi: 10.37201/req/s02.03.2022. Epub 2022 Oct 4. PMID: 36193981; PMCID: PMC9632062.
[4]. Hildebrand D, BÖhringer J, et,al. Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model. Antibiotics (Basel). 2022 Apr 26;11(5):581. doi: 10.3390/antibiotics11050581. PMID: 35625225; PMCID: PMC9137736.
[5]. Ito A, Sato T, et,al. In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01454-17. doi: 10.1128/AAC.01454-17. PMID: 29061741; PMCID: PMC5740388.
[6]. Matsumoto S, Singley CM, et,al. Efficacy of Cefiderocol against Carbapenem-Resistant Gram-Negative Bacilli in Immunocompetent-Rat Respiratory Tract Infection Models Recreating Human Plasma Pharmacokinetics. Antimicrob Agents Chemother. 2017 Aug 24;61(9):e00700-17. doi: 10.1128/AAC.00700-17. PMID: 28630178; PMCID: PMC5571323.
[7]. Ghazi IM, Monogue ML, et,al. Pharmacodynamics of cefiderocol, a novel siderophore cephalosporin, in a Pseudomonas aeruginosa neutropenic murine thigh model. Int J Antimicrob Agents. 2018 Feb;51(2):206-212. doi: 10.1016/j.ijantimicag.2017.10.008. Epub 2017 Oct 27. PMID: 29111435.