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Ceftobiprole

April 12, 2024

Ceftobiprole, sold under the brand name Zevtera among others, is a fifth-generation[5] cephalosporin antibacterial used for the treatment of hospital-acquired pneumonia (excluding ventilator-associated pneumonia) and community-acquired pneumonia. It is marketed by Basilea Pharmaceutica under the brand names Zevtera and Mabelio.[6][7][8][9][10][11] Like other cephalosporins, ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls. Ceftobiprole has high affinity for penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus strains and retains its activity against strains that express divergent mecA gene homologues (mecC or mecALGA251). Ceftobiprole also binds to penicillin-binding protein 2b in Streptococcus pneumoniae (penicillin-intermediate), to penicillin-binding protein 2x in Streptococcus pneumoniae (penicillin-resistant), and to penicillin-binding protein 5 in Enterococcus faecalis.[12]

Ceftobiprole
Clinical data
Trade namesZevtera, Mabelio
Other namesRO0639141-000,[1] BAL9141,[2] ceftobiprole medocaril
AHFS/Drugs.comInternational Drug Names
License data
Routes of
administration		Intravenous
Drug classCephalosporin antibacterial
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)[3]
  • UK: POM (Prescription only)
  • US: ℞-only[4]
  • In general: ℞ (Prescription only)
Identifiers
  • (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
CAS Number
  • 209467-52-7 N
  • 252188-71-9
PubChem CID
  • 6918430
DrugBank
  • DB04918 Y
ChemSpider
  • 23350302 N
UNII
  • 5T97333YZK
KEGG
  • D08885 Y
ChEMBL
  • ChEMBL520642 N
CompTox Dashboard (EPA)
  • DTXSID40870229
ECHA InfoCard100.129.666
Chemical and physical data
FormulaC20H22N8O6S2
Molar mass534.57 g·mol−1
3D model (JSmol)
  • Interactive image
  • C1CNC[C@@H]1N2CC/C(=C\C3=C(N4[C@@H]([C@@H](C4=O)NC(=O)/C(=N\O)/c5nc(sn5)N)SC3)C(=O)O)/C2=O
  • 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/h5,10,12,18,22,34H,1-4,6-7H2,(H,23,29)(H,32,33)(H2,21,24,26)/b8-5+,25-11-/t10-,12-,18-/m1/s1 N
  • Key:VOAZJEPQLGBXGO-SDAWRPRTSA-N N
 NY (what is this?)  (verify)

Medical uses edit

In the US, ceftobiprole is indicated for the treatment of adults with Staphylococcus aureus bloodstream infections (bacteremia) including those with right-sided infective endocarditis;[4] adults with acute bacterial skin and skin structure infections;[4] and people with community-acquired bacterial pneumonia.[4]

Microbiology edit

Ceftobiprole has shown in vitro antimicrobial activity against a broad range of Gram-positive and Gram-negative pathogens. Among the Gram-positive pathogens, ceftobiprole has demonstrated good in vitro activity against methicillin-resistant Staphylococcus aureus, methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, as well as against strains of methicillin-resistant Staphylococcus aureus with reduced susceptibility to linezolid, daptomycin or vancomycin.[13] Ceftobiprole has also displayed potent activity against Streptococcus pneumoniae (including penicillin-sensitive, penicillin-resistant and ceftriaxone-resistant strains) and Enterococcus faecalis, but not against Enterococcus faecium. For Gram-negative pathogens, ceftobiprole has shown good in vitro activity against Haemophilus influenzae (including both ampicillin-susceptible and ampicillin-non-susceptible isolates), Pseudomonas aeruginosa and strains of Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis that do not produce extended-spectrum β-lactamases (ESBL). Like all other cephalosporins, ceftobiprole was inactive against strains that produce extended-spectrum β-lactamases.[14]

The efficacy of ceftobiprole has been demonstrated in two large randomized, double-blind, phase 3 clinical trials in patients with hospital-acquired and community-acquired pneumonia. Ceftobiprole was non-inferior to ceftazidime plus linezolid in the treatment of hospital-acquired pneumonia (excluding ventilator-acquired pneumonia) and non-inferior to ceftriaxone with or without linezolid in the treatment of community-acquired pneumonia.[15][16]

Pharmacology edit

 
Ceftobiprole medocaril
 

Ceftobiprole is the active moiety of the prodrug ceftobiprole medocaril and is available for intravenous treatment only. It is mainly excreted via the kidney.[17]

Society and culture edit

Legal status edit

 
500 mg powder

Ceftobiprole has been approved for the treatment of adults with hospital acquired pneumonia (excluding ventilator-acquired pneumonia) and community-acquired pneumonia in twelve European countries, Canada, and Switzerland.[18]

In February 2010, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a negative opinion, recommending the refusal of the marketing authorization for the medicinal product Zeftera, intended for treatment of complicated skin and soft-tissue infections in adults. The company that applied for authorization is Janssen-Cilag International N.V. The applicant requested a re-examination of the opinion. After considering the grounds for this request, the CHMP re-examined the opinion, and confirmed the refusal of the marketing authorization in June 2010.[19]

References edit

  1. ^ Hebeisen P, Heinze-Krauss I, Angehrn P, Hohl P, Page MG, Then RL (March 2001). "In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci". Antimicrobial Agents and Chemotherapy. 45 (3): 825–836. doi:10.1128/AAC.45.3.825-836.2001. PMC 90381. PMID 11181368.
  2. ^ Jones RN, Deshpande LM, Mutnick AH, Biedenbach DJ (December 2002). "In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci". The Journal of Antimicrobial Chemotherapy. 50 (6): 915–932. doi:10.1093/jac/dkf249. PMID 12461013.
  3. ^ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. from the original on 10 April 2023. Retrieved 10 April 2023.
  4. ^ a b c d https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218275s000lbl.pdf
  5. ^ Scheeren TW (1 January 2015). "Ceftobiprole medocaril in the treatment of hospital-acquired pneumonia". Future Microbiology. 10 (12): 1913–1928. doi:10.2217/fmb.15.115. PMID 26573022.
  6. ^ "Basilea announces distribution agreement with Cardiome to commercialize antibiotic Zevtera/Mabelio (ceftobiprole) in Europe and Israel". Basilea (Press release). 12 September 2017. Retrieved 7 April 2024.
  7. ^ "Basilea to launch Zevtera/Mabelio (ceftobiprole medocaril) in Europe through a commercial services provider" (Press release). Basilea Pharmaceutica. from the original on 31 March 2019. Retrieved 20 September 2016.
  8. ^ "Basilea announces launch of antibiotic Zevtera (ceftobiprole medocaril) in Germany". Basilea (Press release). 5 December 2014. Retrieved 7 April 2024.
  9. ^ "Swissmedic approves Basilea's antibiotic Zevtera (ceftobiprole medocaril) for the treatment of pneumonia". Basilea (Press release). 22 December 2014. Retrieved 7 April 2024.
  10. ^ "Basilea signs exclusive distribution agreement for Zevtera (ceftobiprole medocaril) in the Middle East and North Africa with Hikma Pharmaceuticals LLC". Basilea (Press release). 15 October 2015. Retrieved 7 April 2024.
  11. ^ "Basilea announces that Health Canada approved Zevtera for the treatment of bacterial lung infections". Basilea (Press release). 12 October 2015. Retrieved 7 April 2024.
  12. ^ Syed YY (September 2014). "Ceftobiprole medocaril: a review of its use in patients with hospital- or community-acquired pneumonia". Drugs. 74 (13): 1523–1542. doi:10.1007/s40265-014-0273-x. PMID 25117196. S2CID 2925496.
  13. ^ Zhanel GG, Lam A, Schweizer F, Thomson K, Walkty A, Rubinstein E, et al. (2008). "Ceftobiprole: a review of a broad-spectrum and anti-MRSA cephalosporin". American Journal of Clinical Dermatology. 9 (4): 245–254. doi:10.2165/00128071-200809040-00004. PMID 18572975. S2CID 24357533.
  14. ^ Farrell DJ, Flamm RK, Sader HS, Jones RN (July 2014). "Ceftobiprole activity against over 60,000 clinical bacterial pathogens isolated in Europe, Turkey, and Israel from 2005 to 2010". Antimicrobial Agents and Chemotherapy. 58 (7): 3882–3888. doi:10.1128/AAC.02465-14. PMC 4068590. PMID 24777091.
  15. ^ Farrell DJ, Flamm RK, Sader HS, Jones RN (April 2014). "Activity of ceftobiprole against methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to daptomycin, linezolid or vancomycin, and strains with defined SCCmec types". International Journal of Antimicrobial Agents. 43 (4): 323–327. doi:10.1016/j.ijantimicag.2013.11.005. PMID 24411474.
  16. ^ Nicholson SC, Welte T, File TM, Strauss RS, Michiels B, Kaul P, et al. (March 2012). "A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation". International Journal of Antimicrobial Agents. 39 (3): 240–246. doi:10.1016/j.ijantimicag.2011.11.005. PMID 22230331.
  17. ^ Awad SS, Rodriguez AH, Chuang YC, Marjanek Z, Pareigis AJ, Reis G, et al. (July 2014). "A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia". Clinical Infectious Diseases. 59 (1): 51–61. doi:10.1093/cid/ciu219. PMC 4305133. PMID 24723282.
  18. ^ "Zevtera 500 mg powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC)". (emc). 5 April 2023. Retrieved 1 June 2023.
  19. ^ "Zeftera (previously Zevtera) EPAR". European Medicines Agency (EMA). 18 February 2010. Retrieved 6 April 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

External links edit

  • Clinical trial number NCT03138733 for "Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia" at ClinicalTrials.gov
  • Clinical trial number NCT03137173 for "Ceftobiprole in the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infections" at ClinicalTrials.gov
  • Clinical trial number NCT00326287 for "Ceftobiprole in the Treatment of Patients With Community-Acquired Pneumonia" at ClinicalTrials.gov
  • Clinical trial number NCT03439124 for "Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia" at ClinicalTrials.gov

April 12, 2024
ceftobiprole, sold, under, brand, name, zevtera, among, others, fifth, generation, cephalosporin, antibacterial, used, treatment, hospital, acquired, pneumonia, excluding, ventilator, associated, pneumonia, community, acquired, pneumonia, marketed, basilea, ph. Ceftobiprole sold under the brand name Zevtera among others is a fifth generation 5 cephalosporin antibacterial used for the treatment of hospital acquired pneumonia excluding ventilator associated pneumonia and community acquired pneumonia It is marketed by Basilea Pharmaceutica under the brand names Zevtera and Mabelio 6 7 8 9 10 11 Like other cephalosporins ceftobiprole exerts its antibacterial activity by binding to important penicillin binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls Ceftobiprole has high affinity for penicillin binding protein 2a of methicillin resistant Staphylococcus aureus strains and retains its activity against strains that express divergent mecA gene homologues mecC or mecALGA251 Ceftobiprole also binds to penicillin binding protein 2b in Streptococcus pneumoniae penicillin intermediate to penicillin binding protein 2x in Streptococcus pneumoniae penicillin resistant and to penicillin binding protein 5 in Enterococcus faecalis 12 CeftobiproleClinical dataTrade namesZevtera MabelioOther namesRO0639141 000 1 BAL9141 2 ceftobiprole medocarilAHFS Drugs comInternational Drug NamesLicense dataUS DailyMed CeftobiproleRoutes ofadministrationIntravenousDrug classCephalosporin antibacterialATC codeJ01DI01 WHO Legal statusLegal statusAU S4 Prescription only 3 UK POM Prescription only US only 4 In general Prescription only IdentifiersIUPAC 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 acidCAS Number209467 52 7 N252188 71 9PubChem CID6918430DrugBankDB04918 YChemSpider23350302 NUNII5T97333YZKKEGGD08885 YChEMBLChEMBL520642 NCompTox Dashboard EPA DTXSID40870229ECHA InfoCard100 129 666Chemical and physical dataFormulaC 20H 22N 8O 6S 2Molar mass534 57 g mol 13D model JSmol Interactive imageSMILES C1CNC C H 1N2CC C C C3 C N4 C H C H C4 O NC O C N O c5nc sn5 N SC3 C O O C2 OInChI 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 34H 1 4 6 7H2 H 23 29 H 32 33 H2 21 24 26 b8 5 25 11 t10 12 18 m1 s1 NKey VOAZJEPQLGBXGO SDAWRPRTSA N N N Y what is this verify Contents 1 Medical uses 2 Microbiology 3 Pharmacology 4 Society and culture 4 1 Legal status 5 References 6 External linksMedical uses editIn the US ceftobiprole is indicated for the treatment of adults with Staphylococcus aureus bloodstream infections bacteremia including those with right sided infective endocarditis 4 adults with acute bacterial skin and skin structure infections 4 and people with community acquired bacterial pneumonia 4 Microbiology editCeftobiprole has shown in vitro antimicrobial activity against a broad range of Gram positive and Gram negative pathogens Among the Gram positive pathogens ceftobiprole has demonstrated good in vitro activity against methicillin resistant Staphylococcus aureus methicillin susceptible Staphylococcus aureus and coagulase negative staphylococci as well as against strains of methicillin resistant Staphylococcus aureus with reduced susceptibility to linezolid daptomycin or vancomycin 13 Ceftobiprole has also displayed potent activity against Streptococcus pneumoniae including penicillin sensitive penicillin resistant and ceftriaxone resistant strains and Enterococcus faecalis but not against Enterococcus faecium For Gram negative pathogens ceftobiprole has shown good in vitro activity against Haemophilus influenzae including both ampicillin susceptible and ampicillin non susceptible isolates Pseudomonas aeruginosa and strains of Escherichia coli Klebsiella pneumoniae and Proteus mirabilis that do not produce extended spectrum b lactamases ESBL Like all other cephalosporins ceftobiprole was inactive against strains that produce extended spectrum b lactamases 14 The efficacy of ceftobiprole has been demonstrated in two large randomized double blind phase 3 clinical trials in patients with hospital acquired and community acquired pneumonia Ceftobiprole was non inferior to ceftazidime plus linezolid in the treatment of hospital acquired pneumonia excluding ventilator acquired pneumonia and non inferior to ceftriaxone with or without linezolid in the treatment of community acquired pneumonia 15 16 Pharmacology edit nbsp Ceftobiprole medocaril nbsp Ceftobiprole is the active moiety of the prodrug ceftobiprole medocaril and is available for intravenous treatment only It is mainly excreted via the kidney 17 Society and culture editLegal status edit nbsp 500 mg powderCeftobiprole has been approved for the treatment of adults with hospital acquired pneumonia excluding ventilator acquired pneumonia and community acquired pneumonia in twelve European countries Canada and Switzerland 18 In February 2010 the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a negative opinion recommending the refusal of the marketing authorization for the medicinal product Zeftera intended for treatment of complicated skin and soft tissue infections in adults The company that applied for authorization is Janssen Cilag International N V The applicant requested a re examination of the opinion After considering the grounds for this request the CHMP re examined the opinion and confirmed the refusal of the marketing authorization in June 2010 19 References edit Hebeisen P Heinze Krauss I Angehrn P Hohl P Page MG Then RL March 2001 In vitro and in vivo properties of Ro 63 9141 a novel broad spectrum cephalosporin with activity against methicillin resistant staphylococci Antimicrobial Agents and Chemotherapy 45 3 825 836 doi 10 1128 AAC 45 3 825 836 2001 PMC 90381 PMID 11181368 Jones RN Deshpande LM Mutnick AH Biedenbach DJ December 2002 In vitro evaluation of BAL9141 a novel parenteral cephalosporin active against oxacillin resistant staphylococci The Journal of Antimicrobial Chemotherapy 50 6 915 932 doi 10 1093 jac dkf249 PMID 12461013 Prescription medicines registration of new chemical entities in Australia 2015 Therapeutic Goods Administration TGA 21 June 2022 Archived from the original on 10 April 2023 Retrieved 10 April 2023 a b c d https www accessdata fda gov drugsatfda docs label 2024 218275s000lbl pdf Scheeren TW 1 January 2015 Ceftobiprole medocaril in the treatment of hospital acquired pneumonia Future Microbiology 10 12 1913 1928 doi 10 2217 fmb 15 115 PMID 26573022 Basilea announces distribution agreement with Cardiome to commercialize antibiotic Zevtera Mabelio ceftobiprole in Europe and Israel Basilea Press release 12 September 2017 Retrieved 7 April 2024 Basilea to launch Zevtera Mabelio ceftobiprole medocaril in Europe through a commercial services provider Press release Basilea Pharmaceutica Archived from the original on 31 March 2019 Retrieved 20 September 2016 Basilea announces launch of antibiotic Zevtera ceftobiprole medocaril in Germany Basilea Press release 5 December 2014 Retrieved 7 April 2024 Swissmedic approves Basilea s antibiotic Zevtera ceftobiprole medocaril for the treatment of pneumonia Basilea Press release 22 December 2014 Retrieved 7 April 2024 Basilea signs exclusive distribution agreement for Zevtera ceftobiprole medocaril in the Middle East and North Africa with Hikma Pharmaceuticals LLC Basilea Press release 15 October 2015 Retrieved 7 April 2024 Basilea announces that Health Canada approved Zevtera for the treatment of bacterial lung infections Basilea Press release 12 October 2015 Retrieved 7 April 2024 Syed YY September 2014 Ceftobiprole medocaril a review of its use in patients with hospital or community acquired pneumonia Drugs 74 13 1523 1542 doi 10 1007 s40265 014 0273 x PMID 25117196 S2CID 2925496 Zhanel GG Lam A Schweizer F Thomson K Walkty A Rubinstein E et al 2008 Ceftobiprole a review of a broad spectrum and anti MRSA cephalosporin American Journal of Clinical Dermatology 9 4 245 254 doi 10 2165 00128071 200809040 00004 PMID 18572975 S2CID 24357533 Farrell DJ Flamm RK Sader HS Jones RN July 2014 Ceftobiprole activity against over 60 000 clinical bacterial pathogens isolated in Europe Turkey and Israel from 2005 to 2010 Antimicrobial Agents and Chemotherapy 58 7 3882 3888 doi 10 1128 AAC 02465 14 PMC 4068590 PMID 24777091 Farrell DJ Flamm RK Sader HS Jones RN April 2014 Activity of ceftobiprole against methicillin resistant Staphylococcus aureus strains with reduced susceptibility to daptomycin linezolid or vancomycin and strains with defined SCCmec types International Journal of Antimicrobial Agents 43 4 323 327 doi 10 1016 j ijantimicag 2013 11 005 PMID 24411474 Nicholson SC Welte T File TM Strauss RS Michiels B Kaul P et al March 2012 A randomised double blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community acquired pneumonia requiring hospitalisation International Journal of Antimicrobial Agents 39 3 240 246 doi 10 1016 j ijantimicag 2011 11 005 PMID 22230331 Awad SS Rodriguez AH Chuang YC Marjanek Z Pareigis AJ Reis G et al July 2014 A phase 3 randomized double blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital acquired pneumonia Clinical Infectious Diseases 59 1 51 61 doi 10 1093 cid ciu219 PMC 4305133 PMID 24723282 Zevtera 500 mg powder for concentrate for solution for infusion Summary of Product Characteristics SmPC emc 5 April 2023 Retrieved 1 June 2023 Zeftera previously Zevtera EPAR European Medicines Agency EMA 18 February 2010 Retrieved 6 April 2024 Text was copied from this source which is copyright European Medicines Agency Reproduction is authorized provided the source is acknowledged External links editClinical trial number NCT03138733 for Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia at ClinicalTrials gov Clinical trial number NCT03137173 for Ceftobiprole in the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infections at ClinicalTrials gov Clinical trial number NCT00326287 for Ceftobiprole in the Treatment of Patients With Community Acquired Pneumonia at ClinicalTrials gov Clinical trial number NCT03439124 for Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia at ClinicalTrials gov Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Ceftobiprole amp oldid 1217697733, wikipedia, wiki, book, books, library,

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