Cefiderocol

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Cefiderocol
Cefiderocol.svg
Clinical data
Routes of
administration
Intravenous infusion
ATC code
  • none
Legal status
Legal status
  • Experimental
Pharmacokinetic data
Protein binding56–58%[1]
Elimination half-life2.8 hours
Excretionmainly renal (60–70% unchanged)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC30H34ClN7O10S2
Molar mass752.21 g·mol−1
3D model (JSmol)

Cefiderocol is an experimental parenterally administered siderophore cephalosporin antibiotic aimed at countering multi-drug-resistant Gram-negative bacteria including Pseudomonas aeruginosa.[2][3][4] As of 2018, a phase 2 clinical trial appears to show efficacy similar to or better than imipenem-cilastatin in combating drug-resistant bacteria, and its makers, Shionogi Inc., have stated that they will seek approval for sale and marketing of the drug in a New Drug Application to the U.S. Food and Drug Administration.[4][5][6]

It has been described as a "Trojan-horse antibiotic" for its mechanism of entering bacterial cells by binding to iron, which is actively transported into the bacterial cells along with the cefiderocol.[5][7][8]

Mechanism of action[edit]

It bypasses the bacterial porin channels by using the bacteria's own iron-transport system for being transported in.[9]

References[edit]

  1. ^ Katsube, T.; Echols, R.; Arjona Ferreira, J. C.; Krenz, H. K.; Berg, J. K.; Galloway, C. (2017). "Cefiderocol, a Siderophore Cephalosporin for Gram‐Negative Bacterial Infections: Pharmacokinetics and Safety in Subjects With Renal Impairment". J Clin Pharmacol. 57 (5): 584–591. doi:10.1002/jcph.841. PMC 5412848. PMID 27874971.
  2. ^ Choi, Justin J; McCarthy, Matthew W. (24 January 2018). "Cefiderocol: a novel siderophore cephalosporin". Expert Opinion on Investigational Drugs. 27 (2): 193–197. doi:10.1080/13543784.2018.1426745. PMID 29318906.
  3. ^ Aoki, Toshiaki; Yoshizawa, Hidenori; Yamawaki, Kenji; Yokoo, Katsuki; Sato, Jun; Hisakawa, Shinya; Hasegawa, Yasushi; Kusano, Hiroki; Sano, Masayuki (2018-07-15). "Cefiderocol (S-649266), A new siderophore cephalosporin exhibiting potent activities against Pseudomonas aeruginosa and other gram-negative pathogens including multi-drug resistant bacteria: Structure activity relationship". European Journal of Medicinal Chemistry. 155: 847–868. doi:10.1016/j.ejmech.2018.06.014. ISSN 1768-3254. PMID 29960205.
  4. ^ a b Portsmouth, Simon; van Veenhuyzen, David; Echols, Roger; Machida, Mitsuaki; Ferreira, Juan Camilo Arjona; Ariyasu, Mari; Tenke, Peter; Nagata, Tsutae Den (2018-10-25). "Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial". The Lancet Infectious Diseases. 0. doi:10.1016/S1473-3099(18)30554-1. ISSN 1473-3099.
  5. ^ a b Matthews-King, Alex (2018-10-26). "Antibiotic 'Trojan horse' could defeat superbugs causing global medical crisis, trial finds". The Independent. Retrieved 2018-10-26.
  6. ^ Gallagher, James (2018-10-26). "New 'Trojan horse' antibiotic promising". BBC News. Retrieved 2018-10-26.
  7. ^ Newey, Sarah (2018-10-26). "New 'Trojan horse' drug proves effective against antibiotic resistant bacteria". The Telegraph. ISSN 0307-1235. Retrieved 2018-10-26.
  8. ^ Simpson, Daniel H.; Scott, Peter (2017). "Antimicrobial Metallodrugs". In Lo, Kenneth. Inorganic and Organometallic Transition Metal Complexes with Biological Molecules and Living Cells. Elsevier. ISBN 9780128038871.
  9. ^ Ito, Akinobu; Nishikawa, Toru; Matsumoto, Shuhei; Yoshizawa, Hidenori; Sato, Takafumi; Nakamura, Rio; Tsuji, Masakatsu; Yamano, Yoshinori (10 October 2016). "Siderophore Cephalosporin Cefiderocol Utilizes Ferric Iron Transporter Systems for Antibacterial Activity against". Antimicrobial Agents and Chemotherapy. 60 (12): AAC.01405–16. doi:10.1128/AAC.01405-16. PMC 5119021. PMID 27736756.