Cefiderocol
Identification
- Summary
Cefiderocol is a cephalosporin antibiotic used in complicated urinary tract infections.
- Brand Names
- Fetroja
- Generic Name
- Cefiderocol
- DrugBank Accession Number
- DB14879
- Background
Cefiderocol is a cephalosporin antibacterial drug and exerts a mechanism of action similar to other β-lactam antibiotics.Label Unlike other agents in this category, cefiderocol is a siderophore able to undergo active transport into the bacterial cell through iron channels.2 It represents a significant addition to antibacterial treatment option as it has proven to be effective in vitro against multidrug resistant strains including extended spectrum β-lactamase producers and carbapenemase producing bacteria.
Cefiderocol was granted designation as a Qualified Infectious Disease Product and granted priority review status by the FDA on November 14, 2019.7 It is indicated for use in complicated urinary tract infections in patients with limited or no alternative treatments available.Label This indication was supported by a positive clinical trial composed of 448 patients with complicated urinary tract infections which demonstrated a 72.6% rate of symptom resolution and bacterial eradication with cefiderocol compared to 54.6% with the comparator, imipenem/cilastatin.4 A concern noted in the trial was a 0.3% higher rate of all cause mortality, the cause of which has not been determined.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
- Weight
- Average: 752.21
Monoisotopic: 751.1497104 - Chemical Formula
- C30H34ClN7O10S2
- Synonyms
- Cefiderocol
- External IDs
- GSK 2696266
- GSK2696266
- RSC 649266
- S 649266
- S-649266
Pharmacology
- Indication
Cefiderocol is indicated for the treatment of complicated urinary tract infections with or without pyelonephritis.Label
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- Pharmacodynamics
Similarly to other cephalosporins, cefiderocol exerts bactericidal activity against a range of bacterial species.Label,2 Cefiderocol has primarily shown efficacy against aerobic Gram negative bacteria including Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa.2
- Mechanism of action
Cefiderocol acts by binding to and inhibiting penicillin-binding proteins (PBPs), preventing cell wall synthesis and ultimately causing death of the bacterial cell.Label,2 Like other β-lactam antibiotics cefiderocol is able to enter bacterial cells via passive diffusion through porins.3,Label Unlike other β-lactams, cefiderocol contains a chlorocatechol group which allows it to chelate iron. Once bound to ferric iron cefiderocol is able to undergo active transport into bacterial cells through iron channels in the outer cell membrane such as those encoded by the cirA and fiu genes in E. coli or the PiuA gene in P. aeruginosa. Once inside the cell, cefiderocol binds to and inhibits PBP3 with high affinity thereby preventing the linking of peptodoglycan layers via the pentapeptide bridge.Label,2,5 PBP1a, 1b, 2,and 4 are also bound and inhibited by cefiderocol but with a lesser potency than PBP3 and are therefore expected to contribute less to its antibacterial effect.
Target Actions Organism APenicillin-binding protein 3 inhibitorPseudomonas aeruginosa APenicillin-binding protein 1A inhibitorPseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228) APenicillin-binding protein 1B inhibitorPseudomonas aeruginosa APenicillin-binding protein 2 inhibitorPseudomonas aeruginosa AD-alanyl-D-alanine carboxypeptidase DacB inhibitorEscherichia coli (strain K12) - Absorption
A single intravenous dose of 2 g of cefiderocol in healthy patients produces a Cmax of 89.7 mg/L and an AUC of 386 mg*h/L.Label In patients with complicated urinary tract infections and a creatinine clearance of at least 60 mL/min, doses of 2 g cefiderocol every 8 hours produced an AUC of 394.7 mg*h/L and a Cmax of 138 mg/L. However the infusion rate for this chronic dosing was 3 times the recommended rate. Cmax and AUC are known to increase proportionally with dosage.
- Volume of distribution
Cefiderocol has a mean volume of distribution of 18 L.Label
- Protein binding
Cefiderocol is 40-60% bound to plasma proteins, predominantly to albumin.Label
- Metabolism
Cefiderocol undergoes a small degree of metabolism to a cefiderocol epimer at the 7 position, cefiderocol catechol-3-methoxy and -4-methoxy, and a pyrrolidine chlorobenzamide product (PCBA).1 PCBA undergoes further metabolism to sulfated, methylated, and glucuronidated metabolites. The enzymes involved in these reactions have yet to be identified and cefiderocol has not been shown to interfere in the metabolism of other agents.Label
- Route of elimination
98.6% of cefiderocol is eliminated in the urine with 90.6% as the unchanged parent drug.Label The remaining 8% is eliminated as metabolites. 2.8% is eliminated in the feces. Less than 10% of cefiderocol is metabolized.
- Half-life
The terminal elimination half-life of cefiderocol is 2-3 h.Label
- Clearance
Cefiderocol has a mean clearance of 5.18 L/h.Label
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Information on cefiderocol toxicity is not yet available. In case of overdose supportive care is recommended.Label Hemodialysis has proven effective in removing cefiderocol with a 3-4 hour session removing 60% of circulating drug.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Cefiderocol sulfate tosylate TTP8LBP45D 2135543-94-9 QNMVZYPDWLKAJC-RXVBEKIDSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Fetcroja Injection, powder, for solution 1 g Intravenous Shionogi B.V. 2021-03-17 Not applicable EU Fetroja Injection, powder, for solution 1 g/10mL Intravenous SHIONOGI INC. 2020-01-31 Not applicable US
Categories
- ATC Codes
- J01DI04 — Cefiderocol
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Pseudomonas aeruginosa
- Streptococcus pyogenes
- Streptococcus pneumoniae
- Neisseria meningitidis
- Haemophilus influenzae
- Neisseria gonorrhoeae
- Campylobacter jejuni
- Escherichia coli
- Salmonella typhi
- Moraxella catarrhalis
- Serratia marcescens
- Proteus vulgaris
- Proteus mirabilis
- Providencia stuartii
- Providencia rettgeri
- Morganella morganii
- Enterobacter cloacae
- Klebsiella pneumoniae
- Klebsiella oxytoca
- Salmonella paratyphi
- Shigella flexneri
- Pseudomonas putida
- Citrobacter freundii
- Yersinia enterocolitica
- Pseudomonas stutzeri
- Acinetobacter calcoaceticus
- Salmonella typhimurium
- Micrococcus luteus
- Salmonella enteritidis
- Aeromonas hydrophila
- Acinetobacter baumannii
- Elizabethkingia meningoseptica
- Stenotrophomonas maltophilia
- Acinetobacter johnsonii
- Acinetobacter haemolyticus
- Acinetobacter lwoffii
- Salmonella choleraesuis
- Vibrio fluvialis
- Vibrio vulnificus
- Yersinia pseudotuberculosis
Chemical Identifiers
- UNII
- SZ34OMG6E8
- CAS number
- 1225208-94-5
- InChI Key
- DBPPRLRVDVJOCL-FQRUVTKNSA-N
- InChI
- InChI=1S/C30H34ClN7O10S2/c1-30(2,28(46)47)48-36-19(16-13-50-29(32)34-16)24(42)35-20-25(43)37-21(27(44)45)14(12-49-26(20)37)11-38(8-3-4-9-38)10-7-33-23(41)15-5-6-17(39)22(40)18(15)31/h5-6,13,20,26H,3-4,7-12H2,1-2H3,(H7-,32,33,34,35,36,39,40,41,42,44,45,46,47)/t20-,26-/m1/s1
- IUPAC Name
- 1-{[(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetamido]-2-carboxylato-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl}-1-{2-[(2-chloro-3,4-dihydroxyphenyl)formamido]ethyl}pyrrolidin-1-ium
- SMILES
- [H][C@]12SCC(C[N+]3(CCNC(=O)C4=C(Cl)C(O)=C(O)C=C4)CCCC3)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC(N)=N1)C([O-])=O
References
- General References
- Miyazaki S, Katsube T, Shen H, Tomek C, Narukawa Y: Metabolism, Excretion, and Pharmacokinetics of [(14) C]-Cefiderocol (S-649266), a Siderophore Cephalosporin, in Healthy Subjects Following Intravenous Administration. J Clin Pharmacol. 2019 Jul;59(7):958-967. doi: 10.1002/jcph.1386. Epub 2019 Feb 7. [Article]
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
- Kobayashi Y, Takahashi I, Nakae T: Diffusion of beta-lactam antibiotics through liposome membranes containing purified porins. Antimicrob Agents Chemother. 1982 Nov;22(5):775-80. doi: 10.1128/aac.22.5.775. [Article]
- Portsmouth S, van Veenhuyzen D, Echols R, Machida M, Ferreira JCA, Ariyasu M, Tenke P, Nagata TD: 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. Lancet Infect Dis. 2018 Dec;18(12):1319-1328. doi: 10.1016/S1473-3099(18)30554-1. Epub 2018 Oct 25. [Article]
- Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
- ChemSpider: Cefiderocol [Link]
- FDA Press Release Cefiderocol [Link]
- External Links
- ChemSpider
- 52084902
- 2265702
- ChEMBL
- CHEMBL3989974
- Wikipedia
- Cefiderocol
- FDA label
- Download (387 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, for solution Intravenous 1 G Injection, powder, for solution Intravenous 1 g/10mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9238657 No 2016-01-19 2031-11-19 US US10004750 No 2018-06-26 2035-09-03 US US9949982 No 2018-04-24 2035-09-03 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP -2.265 ChemSpider: Cefiderocol - Predicted Properties
Property Value Source Water Solubility 0.00201 mg/mL ALOGPS logP 1.84 ALOGPS logP -2.9 Chemaxon logS -5.6 ALOGPS pKa (Strongest Acidic) 2.64 Chemaxon pKa (Strongest Basic) 4.05 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 13 Chemaxon Hydrogen Donor Count 6 Chemaxon Polar Surface Area 256.9 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 204.1 m3·mol-1 Chemaxon Polarizability 72.74 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
Targets

- Kind
- Protein
- Organism
- Pseudomonas aeruginosa
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Known to bind to PBP3 of E. coli NIHJ JC-2, K. pneumoniae SR22291, P. aeruginosa ATCC 27853, and A. baumannii ATCC 17978.
- General Function
- Peptidoglycan glycosyltransferase activity
- Specific Function
- Not Available
- Gene Name
- pbpB
- Uniprot ID
- Q51504
- Uniprot Name
- Cell division protein
- Molecular Weight
- 62855.78 Da
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
- Kind
- Protein
- Organism
- Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Known to bind to PBP1a of E. coli NIHJ JC-2, K. pneumoniae SR22291, and P. aeruginosa ATCC 27853. May bind to either PBP1a, PBP1b or both of A. baumannii ATCC 17978.
- General Function
- Transferase activity, transferring glycosyl groups
- Specific Function
- Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
- Gene Name
- mrcA
- Uniprot ID
- Q07806
- Uniprot Name
- Penicillin-binding protein 1A
- Molecular Weight
- 91198.715 Da
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
- Kind
- Protein
- Organism
- Pseudomonas aeruginosa
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Known to bind to PBP1b of E. coli NIHJ JC-2, K. pneumoniae SR22291, and P. aeruginosa ATCC 27853. May bind to either PBP1a, PBP1b or both of A. baumannii ATCC 17978.
- General Function
- Peptidoglycan glycosyltransferase activity
- Specific Function
- Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
- Gene Name
- ponB
- Uniprot ID
- Q9X6W0
- Uniprot Name
- Penicillin-binding protein 1B
- Molecular Weight
- 85486.615 Da
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
- Kind
- Protein
- Organism
- Pseudomonas aeruginosa
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Known to bind to PBP3 of E. coli NIHJ JC-2, K. pneumoniae SR22291, and P. aeruginosa ATCC 27853, and A. baumannii ATCC 17978.
- General Function
- Penicillin binding
- Specific Function
- Not Available
- Gene Name
- pbpA
- Uniprot ID
- Q9X6V3
- Uniprot Name
- Penicillin-binding protein 2
- Molecular Weight
- 72212.855 Da
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- Known to bind to PBP4 of E. coli NIHJ JC-2, K. pneumoniae SR22291, and P. aeruginosa ATCC 27853.
- General Function
- Serine-type d-ala-d-ala carboxypeptidase activity
- Specific Function
- Not involved in transpeptidation but exclusively catalyzes a DD-carboxypeptidase and DD-endopeptidase reaction.
- Gene Name
- dacB
- Uniprot ID
- P24228
- Uniprot Name
- D-alanyl-D-alanine carboxypeptidase DacB
- Molecular Weight
- 51797.85 Da
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Ligand
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
Transporters
- Kind
- Protein group
- Organism
- Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Drug transmembrane transporter activity
- Specific Function
- The periplasmic linker component of the MexAB-OprM efflux system that confers multidrug resistance. Also functions as the major efflux pump for n-hexane and p-xylene efflux. Over-expression of the ...
Components:
Name | UniProt ID |
---|---|
Multidrug resistance protein MexA | P52477 |
Multidrug resistance protein MexB | P52002 |
Outer membrane protein OprM | Q51487 |
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Cefiderocol acts as a substrate when bound to iron.
- General Function
- Involved in the active transport across the outer membrane of iron complexed with catecholate siderophores such as dihydroxybenzoylserine and dihydroxybenzoate. It derives its energy for transport by interacting with the trans-periplasmic membrane protein TonB. Can also transport catechol-substituted cephalosporins. Receptor for microcins M, H47 and E492.
- Specific Function
- Siderophore uptake transmembrane transporter activity
- Gene Name
- fiu
- Uniprot ID
- P75780
- Uniprot Name
- Catecholate siderophore receptor Fiu
- Molecular Weight
- 81959.515 Da
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
- Kind
- Protein
- Organism
- Escherichia coli (strain K12)
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Cefiderocol acts as a substrate when bound to iron.
- General Function
- Siderophore transmembrane transporter activity
- Specific Function
- Not yet known. Postulated to participate in iron transport. Outer membrane receptor for colicins IA and IB.
- Gene Name
- cirA
- Uniprot ID
- P17315
- Uniprot Name
- Colicin I receptor
- Molecular Weight
- 73895.2 Da
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
- Kind
- Protein
- Organism
- Pseudomonas aeruginosa (strain UCBPP-PA14)
- Pharmacological action
- No
- Actions
- Substrate
- Curator comments
- Cefiderocol acts as a substrate when bound to iron.
- General Function
- Not Available
- Specific Function
- Siderophore uptake transmembrane transporter activity
- Gene Name
- piuA
- Uniprot ID
- A0A0H2ZGX7
- Uniprot Name
- Putative outer membrane ferric siderophore receptor
- Molecular Weight
- 82344.98 Da
References
- Ito A, Sato T, Ota M, Takemura M, Nishikawa T, Toba S, Kohira N, Miyagawa S, Ishibashi N, Matsumoto S, Nakamura R, Tsuji M, Yamano Y: In Vitro Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: AAC.01454-17. doi: 10.1128/AAC.01454-17. Print 2018 Jan. [Article]
Drug created at May 20, 2019 14:32 / Updated at February 21, 2021 18:54