Cefiderocol (S-649266)|1225208-94-5|安捷凯

Background

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].

参考文献:
[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, B?hringer 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.

Cefiderocol是一种新型铁载体头孢菌素，对革兰氏阴性菌和非发酵革兰氏阴性菌具有较强的体外活性[1-3]。

Cefiderocol(10/40/70 mg/L；3 天）抑制 LPS 刺激的促炎细胞因子的产生[4]。铜绿假单胞菌中铁转运体 PiuA 或大肠杆菌中 CirA 和 Fiu 的缺失导致头孢地尔考 MIC 增加 16 倍，表明这些铁转运体有助于头孢地尔考穿过外膜[5]。

每 8 小时给予 2 克头孢地尔考 3 小时输注 4 天，使大鼠肺部感染的铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯菌的碳青霉烯类耐药菌株的细胞减少了 3 log10 以上[6 ].头孢地尔考在白细胞减少小鼠大腿感染模型中的药效学呈S型剂量-反应曲线，随着剂量的增加杀菌效果更好[7]。

Protocol

Cell experiment [1]:

Cell lines

Peripheral blood mononuclear cells (PBMCs)

Preparation Method

Cells were stimulated with 100 ng/mL LPS with or without cefiderocol (10 mg/L, 40 mg/L, 70 mg/L) for 3 days

Reaction Conditions

10/40/70 mg/L;3 days

Applications

Higher concentrations of cefiderocol inhibit the production of lipopolysaccharide-stimulated proinflammatory cytokines.

Animal experiment [2]:

Animal models

Pathogen-free male Sprague-Dawley rats

Preparation Method

Inoculants of 0.1 ml(Pseudomonas aeruginosa) or 0.2 ml(Pseudomonas baumannii or Klebsiella pneumoniae) were injected into the lungs of rats to induce respiratory infection, The infected rats were given cefiderocol subcutaneously.

Dosage form

2 g every 8 h as a 3-h infusion for 4 days

Applications

参考文献:

[1]. Hildebrand D, B?hringer 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.
[2].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.

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Cefiderocol (S-649266)

Cefiderocol (S-649266)详情

Background

Protocol

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