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
Pregnancy cat.  ?
Legal status  ?
Routes Intravenous
Identifiers
CAS number 209467-52-7 N
252188-71-9 (medocaril)
ATC code J01DI01 [1]
PubChem CID 6918430
ChemSpider 21106277 Y
UNII 5T97333YZK Y
KEGG D08885 Y
ChEMBL CHEMBL407727 N
Chemical data
Formula C20H22N8O6S2 
Mol. mass 534.568 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Ceftobiprole (Zeftera/Zevtera) is a 4th 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 non-inferior to the combination of vancomycin and ceftazidime for the treatment of skin and soft tissue infections.

It has been described as a "fifth generation" cephalosporin,[8][9] though acceptance for this terminology is not universal.

Contents

Pharmacology

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]

Dosing

Ceftobiprole cannot be given by mouth and so is given intravenously. It is not FDA approved to be used in children.[5]

Ceftobiprole has been approved for use in Canada and Switzerland, and is under review by regulatory authorities in the United States, the European Union, Australia, Russia and South Africa.[10] In November 2008 the US FDA declined to approve Ceftobiprole citing data integrity concerns with two of the supporting studies,[11] and prompting Basilea to sue Johnson & Johnson for breach of license agreement on February 2009.[12]

Synonyms

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. http://www.whocc.no/atcddd/new_atc_ddd.html#ATCDDD_FINAL. 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. doi:10.1016/j.diagmicrobio.2007.06.023. PMID 17911001. 
  4. ^ a b 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. ^ a b 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. ^ a b c 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=90381. 
  7. ^ Basilea.com
  8. ^ 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. PMID 18225983. http://www.journals.uchicago.edu/doi/abs/10.1086/526528?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dncbi.nlm.nih.gov. 
  9. ^ 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. http://journals.elsevierhealth.com/retrieve/pii/S0891-8422(07)00026-2. 
  10. ^ Basilea superbug drug approved in Canada, Reuters News, June 30, 2008
  11. ^ http://www.dancewithshadows.com/pillscribe/ceftobiprole-antibiotic-to-fight-tougher-bacterial-infections-fails-to-win-approval-in-us/
  12. ^ "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. http://www.basilea.com/News-and-Media/FDA-issues-ceftobiprole-Complete-Response-Letter/317. Retrieved February 2, 2010. 
  13. ^ 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. http://jac.oxfordjournals.org/cgi/content/full/50/6/915?ijkey=44287b37747e341869bed979dc42b8250ff5c6ce. 
Intracellular
inhibit peptidoglycan subunit synthesis and transport: NAM synthesis inhibition (Fosfomycin) • DADAL/AR inhibitors (Cycloserine) • bactoprenol inhibitors (Bacitracin)
Glycopeptide
inhibit PG chain elongation: Vancomycin# (Oritavancin, Telavancin) • Teicoplanin (Dalbavancin) • Ramoplanin
β-lactams/
(inhibit PBP
cross-links)
Ceftobiprole • Ceftaroline fosamil
Combinations
Other

M: BAC

bact (clas)

gr+f/gr+a(t)/gr-p(c)/gr-o

drug(J1p, w, n, m, vacc)