Ceftobiprole

Ceftobiprole

Systematic (IUPAC) name
(6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-ylidene)- 2-nitroso-1-oxoethyl]amino]-8-oxo-3-[(E)-[2-oxo-1-[(3R)- 3-pyrrolidinyl]-3-pyrrolidinylidene]methyl]-5-thia-1- azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Clinical data
AHFS/Drugs.com	International Drug Names
Routes of administration	Intravenous
Legal status
Legal status	Withdrawn from the Canadian market; still marketed in Russia
Identifiers
CAS Number	209467-52-7 252188-71-9 (medocaril)
ATC code	J01DI01 (WHO) [1]
PubChem	CID 6918430
ChemSpider	21106277
UNII	5T97333YZK
KEGG	D08885
ChEMBL	CHEMBL520642
Chemical data
Formula	C20H22N8O6S2
Molar mass	534.568 g/mol
SMILES O=C3N1/C(=C(\CS[C@@H]1[C@@H]3NC(=O)C(\N=O)=C2/NSC(\N)=N2)/C=C4\CCN(C4=O)[C@@H]5CCNC5)C(O)=O
InChI InChI=1S/C20H22N8O6S2/c21-20-24-14(26-36-20)11(25-34)15(29)23-12-17(31)28-13(19(32)33)9(7-35-18(12)28)5-8-2-4-27(16(8)30)10-1-3-22-6-10/h5,10,12,18,22,26H,1-4,6-7H2,(H2,21,24)(H,23,29)(H,32,33)/b8-5+,14-11+/t10-,12-,18-/m1/s1 Key:LXLDMYXULSBRCX-KOGKARRDSA-N
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Ceftobiprole (Zeftera/Zevtera) is a fifth-generation^[2] cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, Pseudomonas aeruginosa, and enterococci.^[3][4][5] It was discovered by Basilea Pharmaceutica^[6] and was developed by Johnson & Johnson Pharmaceutical Research and Development.^[7] It has been shown to be statistically noninferior to the combination of vancomycin and ceftazidime for the treatment of skin and soft tissue infections.^[8]

It has been described as a fifth-generation cephalosporin,^[9][10] though acceptance for this terminology is not universal.

Pharmacology

Like other cephalosporins, ceftobiprole inhibits bacterial growth by blocking penicillin-binding protein, a key enzyme involved in cell wall synthesis. Ceftobiprole inhibits the 2a penicillin-binding protein (PBP) of methicillin-resistant Staphylococcus aureus and the 2x PBP of Streptococcus pneumoniae,^[4] as well as the classic PBP-2 of MSSA. Ceftobiprole is resistant to staphylococcal β-lactamase.^[6]

Mode of administration

Ceftobiprole is given intravenously; it cannot be given by mouth.

Regulatory approvals

Ceftobiprole has been approved for use in Canada, Switzerland, and the European Union.^[11] It is under review by regulatory authorities in the United States, Australia, Russia, and South Africa.^[12] In November 2008, the US FDA declined to approve ceftobiprole, citing data integrity concerns with two of the supporting studies,^[13] and prompting Basilea to sue Johnson & Johnson for breach of license agreement on February 2009.^[14]

Synonyms

• RO0639141-000^[6]
• BAL9141^[15]
• Ceftobiprole medocaril

References

1. WHO International Working Group for Drug Statistics Methodology (August 27, 2008). "ATC/DDD Classification (FINAL): New ATC 5th level codes". WHO Collaborating Centre for Drug Statistics Methodology. Retrieved 2008-09-05.
2. Kollef MH (December 2009). "New antimicrobial agents for methicillin-resistant Staphylococcus aureus". Crit Care Resusc 11 (4): 282–6. PMID 20001879.
3. Yun HC, Ellis MW, Jorgensen JH (2007). "Activity of ceftobiprole against community-associated methicillin-resistant Staphylococcus aureus isolates recently recovered from US military trainees". Diagnostic Microbiology and Infectious Disease 59 (4): 463–6. doi:10.1016/j.diagmicrobio.2007.06.023. PMID 17911001.
4. Widmer A (2008). "Ceftobiprole: A new option for treatment of skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus". Clin Infect Dis 46 (5): 656–8. doi:10.1086/526528. PMID 18225983.
5. Noel GJ, Bush K, Bagchi P, Ianus J, Strauss RS (2008). "A randomized, double-blind trial comparing ceftobiprole medocaril with vancomycin plus ceftazidime plus ceftazidime for the treatment of patients with complicated skin and skin-structure infections". Clin Infect Dis 46 (5): 647–55. doi:10.1086/526527. PMID 18225981.
6. Hebeisen P, Heinze-Krauss I, Angehrn P; et al. (2001). "In vitro and in vivo properties of Ro63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci". Antimicrob Agents Chemother 45 (3): 825–36. doi:10.1128/AAC.45.3.825-836.2001. PMC: 90381. PMID 11181368.
7. Basilea.com
8. Noel, Gary J.; Karen Bush; Partha Bagchi; Juliana Ianus; Richard S. Strauss (2008). "A Randomized, Double-Blind Trial Comparing Ceftobiprole Medocaril with Vancomycin plus Ceftazidime for the Treatment of Patients with Complicated Skin and Skin-Structure Infections". Clin Infect Dis. 46 (5): 647–655. doi:10.1086/526527. PMID 18225981.
9. Widmer AF (March 2008). "Ceftobiprole: a new option for treatment of skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus". Clin. Infect. Dis. 46 (5): 656–8. doi:10.1086/526528. JSTOR 40307068. PMID 18225983 – via JSTOR. (registration required (help)).
10. Kosinski MA, Joseph WS (July 2007). "Update on the treatment of diabetic foot infections". Clin Podiatr Med Surg 24 (3): 383–96, vii. doi:10.1016/j.cpm.2007.03.009. PMID 17613382.
11. Basilea antibiotic to treat pneumonia wins European backing. Reuters, ZURICH | Wed Oct 23, 2013.
12. Basilea superbug drug approved in Canada, Reuters News, June 30, 2008
13. http://www.dancewithshadows.com/pillscribe/ceftobiprole-antibiotic-to-fight-tougher-bacterial-infections-fails-to-win-approval-in-us/
14. "Basilea Pharmaceutica Ltd. announces that the U.S. Food and Drug Administration (FDA) issued to the sponsor, Johnson & Johnson Pharmaceutical Research and Development, L.L.C. (Johnson & Johnson PRD), a Complete Response Letter on ceftobiprole for the treatment of complicated skin and skin structure infections (cSSSI" (Press release). Basilea Pharmaceutica. 2009-07-02. Retrieved February 2, 2010.
15. Jones RN, Deshpande LM, Mutnick AH, Biedenbach DJ (2002). "In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci". J Antimicrob Chemother 50 (6): 915–932. doi:10.1093/jac/dkf249. PMID 12461013.