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{{Short description|Chemical compound}} |
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{{Drugbox |
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{{Use dmy dates|date=April 2024}} |
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| IUPAC_name = (6''R'',7''R'')-7-<nowiki>amino]-8-oxo-3--3-pyrrolidinylidene]methyl]-5-thia-1- azabicyclooct-2-ene-2-carboxylic acid |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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| image = ceftobiprole structure.png |
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{{Infobox drug |
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| ChemSpiderID = 21106277 |
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| Verifiedfields = changed |
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| InChI = 1/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 |
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| Watchedfields = changed |
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| smiles = O=C3N1/C(=C(\CS13NC(=O)C(\N=O)=C2/NSC(\N)=N2)/C=C4\CCN(C4=O)5CCNC5)C(O)=O |
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| verifiedrevid = 460024985 |
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| InChIKey = LXLDMYXULSBRCX-KOGKARRDBO |
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| image = Ceftobiprole2DCSD.svg |
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| InChI1 = 1/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 |
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| width = 300 |
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| StdInChI = 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 |
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| alt = |
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| StdInChIKey = LXLDMYXULSBRCX-KOGKARRDSA-N |
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| CAS_number = 209467-52-7 |
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<!-- Clinical data --> |
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| CAS_supplemental = <br/>{{CAS|252188-71-9}} (medocaril) |
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| ATC_prefix = J01 |
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| pronounce = |
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| tradename = Zevtera, Mabelio |
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| ATC_suffix = DI01 |
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| Drugs.com = {{drugs.com|parent|Zevtera}} |
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| ATC_supplemental = <ref>{{cite web |url=http://www.whocc.no/atcddd/new_atc_ddd.html#ATCDDD_FINAL |title=ATC/DDD Classification (FINAL): New ATC 5th level codes |date=August 27, 2008 |author=WHO International Working Group for Drug Statistics Methodology |publisher=WHO Collaborating Centre for Drug Statistics Methodology |accessdate=2008-09-05}}</ref> |
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| PubChem = 6918430 |
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| MedlinePlus = |
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| DrugBank = |
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| DailyMedID = Ceftobiprole |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU_comment = |
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| pregnancy_category = |
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| routes_of_administration = ] |
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| class = ] |
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| ATC_prefix = J01 |
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| ATC_suffix = DI01 |
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| ATC_supplemental = |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new chemical entities in Australia, 2015 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2015 | access-date=10 April 2023 | archive-date=10 April 2023 | archive-url=https://web.archive.org/web/20230410065829/https://www.tga.gov.au/prescription-medicines-registration-new-chemical-entities-australia-2015 | url-status=live }}</ref> |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F --> |
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| legal_BR_comment = |
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| legal_CA = Rx-only |
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| legal_CA_comment = <ref>{{cite web | title=Zevtera Product information | website=] | date=23 April 2010 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=79864 | access-date=13 April 2024 | archive-date=19 February 2024 | archive-url=https://web.archive.org/web/20240219222432/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=79864 | url-status=live }}</ref><ref>{{cite web | title=Zevtera Product information | website=] | date=20 March 2018 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=93212 | access-date=13 April 2024 | archive-date=30 April 2024 | archive-url=https://web.archive.org/web/20240430024543/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=93212 | url-status=live }}</ref> |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled --> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = POM |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name ="Zevtera FDA label">{{Cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218275s000lbl.pdf |title=Zevtera (ceftobiprole medocaril sodium for injection), for intravenous use |access-date=6 April 2024 |archive-date=6 April 2024 |archive-url=https://web.archive.org/web/20240406064814/https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/218275s000lbl.pdf |url-status=live }}</ref> |
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| legal_EU = |
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| legal_EU_comment = |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> |
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| legal_UN_comment = |
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| legal_status = Rx-only |
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<!-- Pharmacokinetic data --> |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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| metabolites = |
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| onset = |
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| elimination_half-life = |
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| duration_of_action = |
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| excretion = |
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<!-- Identifiers --> |
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| index2_label = as medocaril |
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| CAS_number_Ref = {{cascite|changed|??}} |
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| CAS_number = 209467-52-7 |
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| CAS_number2 = 252188-71-9 |
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| CAS_supplemental = |
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| PubChem = 6918430 |
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| PubChem2 = 135413543 |
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| IUPHAR_ligand = |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB04918 |
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| DrugBank2 = DB14733 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 23350302 |
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| ChemSpiderID2 = 30791463 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = 5T97333YZK |
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| UNII2 = N99027V28J |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D08885 |
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| KEGG = D08885 |
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| KEGG2 = D08886 |
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| ChEBI = |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 520642 |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = RO0639141-000,<ref name="2001Hebeisen">{{cite journal | vauthors = Hebeisen P, Heinze-Krauss I, Angehrn P, Hohl P, Page MG, Then RL | title = In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci | journal = Antimicrobial Agents and Chemotherapy | volume = 45 | issue = 3 | pages = 825–836 | date = March 2001 | pmid = 11181368 | pmc = 90381 | doi = 10.1128/AAC.45.3.825-836.2001 }}</ref> BAL9141,<ref>{{cite journal | vauthors = Jones RN, Deshpande LM, Mutnick AH, Biedenbach DJ | title = In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci | journal = The Journal of Antimicrobial Chemotherapy | volume = 50 | issue = 6 | pages = 915–932 | date = December 2002 | pmid = 12461013 | doi = 10.1093/jac/dkf249 | doi-access = free }}</ref> ceftobiprole medocaril |
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<!-- Chemical and physical data --> |
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| IUPAC_name = (6''R'',7''R'')-7-<nowiki>amino]-8-oxo-3--3-pyrrolidinylidene]methyl]-5-thia-1- azabicyclooct-2-ene-2-carboxylic acid |
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| C=20 | H=22 | N=8 | O=6 | S=2 |
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| C=20 | H=22 | N=8 | O=6 | S=2 |
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| SMILES = C1CNC1N2CC/C(=C\C3=C(N4((C4=O)NC(=O)/C(=N\O)/c5nc(sn5)N)SC3)C(=O)O)/C2=O |
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| molecular_weight = 534.568 g/mol |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| bioavailability = |
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| StdInChI = 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 |
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| protein_bound = |
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| metabolism = |
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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| elimination_half-life = |
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| StdInChIKey = VOAZJEPQLGBXGO-SDAWRPRTSA-N |
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| excretion = |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| density = |
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| density_notes = |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| melting_point = |
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| pregnancy_category= |
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| melting_high = |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| melting_notes = |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| boiling_point = |
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| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> |
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| boiling_notes = |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_status = |
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| solubility = |
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| sol_units = |
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| routes_of_administration = Intravenous |
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| specific_rotation = |
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}} |
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}} |
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'''Ceftobiprole''', sold under the brand name '''Zevtera''' among others, is a fifth-generation<ref>{{cite journal | vauthors = Scheeren TW | title = Ceftobiprole medocaril in the treatment of hospital-acquired pneumonia | journal = Future Microbiology | volume = 10 | issue = 12 | pages = 1913–1928 | date = 1 January 2015 | pmid = 26573022 | doi = 10.2217/fmb.15.115 | doi-access = free }}</ref> ] used for the treatment of ] (excluding ventilator-associated pneumonia) and ]. It is marketed by ] under the brand names Zevtera and Mabelio.<ref>{{cite press release | title=Basilea announces distribution agreement with Cardiome to commercialize antibiotic Zevtera/Mabelio (ceftobiprole) in Europe and Israel | website=Basilea | date=12 September 2017 | url=https://www.basilea.com/news/basilea-to-launch-zevterar-mabelior-ceftobiprole-medocaril-in-europe-through-a-commercial-services-provider?type=1546938654 | access-date=7 April 2024 | archive-date=7 April 2024 | archive-url=https://web.archive.org/web/20240407013938/https://www.basilea.com/news/basilea-to-launch-zevterar-mabelior-ceftobiprole-medocaril-in-europe-through-a-commercial-services-provider?type=1546938654 | url-status=live }}</ref><ref>{{cite press release | url=http://www.basilea.com/News-and-Media/Basilea-to-launch-Zevtera-Mabelio-ceftobiprole-medocaril-in-Europe-through-a-commercial-services-provider/7dcfb10b-c4ef-5a82-8359-f88b1f36cb96/ | title=Basilea to launch Zevtera/Mabelio (ceftobiprole medocaril) in Europe through a commercial services provider | publisher=Basilea Pharmaceutica | access-date=20 September 2016 | archive-url=https://web.archive.org/web/20190331140355/http://www.basilea.com/News-and-Media/Basilea-to-launch-Zevtera-Mabelio-ceftobiprole-medocaril-in-Europe-through-a-commercial-services-provider/7dcfb10b-c4ef-5a82-8359-f88b1f36cb96/ | archive-date=31 March 2019 | url-status=live }}</ref><ref>{{cite press release | title=Basilea announces launch of antibiotic Zevtera (ceftobiprole medocaril) in Germany | website=Basilea | date=5 December 2014 | url=https://www.basilea.com/news/basilea-announces-launch-of-antibiotic-zevterar-ceftobiprole-medocaril-in-germany?type=1546938654 | access-date=7 April 2024 | archive-date=7 April 2024 | archive-url=https://web.archive.org/web/20240407013939/https://www.basilea.com/news/basilea-announces-launch-of-antibiotic-zevterar-ceftobiprole-medocaril-in-germany?type=1546938654 | url-status=live }}</ref><ref>{{cite press release | title=Swissmedic approves Basilea's antibiotic Zevtera (ceftobiprole medocaril) for the treatment of pneumonia | website=Basilea | date=22 December 2014 | url=https://www.basilea.com/news/swissmedic-approves-basileas-antibiotic-zevterar-ceftobiprole-medocaril-for-the-treatment-of-pneumonia?type=1546938654 | access-date=7 April 2024 | archive-date=7 April 2024 | archive-url=https://web.archive.org/web/20240407013939/https://www.basilea.com/news/swissmedic-approves-basileas-antibiotic-zevterar-ceftobiprole-medocaril-for-the-treatment-of-pneumonia?type=1546938654 | url-status=live }}</ref><ref>{{cite press release | title=Basilea signs exclusive distribution agreement for Zevtera (ceftobiprole medocaril) in the Middle East and North Africa with Hikma Pharmaceuticals LLC | website=Basilea | date=15 October 2015 | url=https://www.basilea.com/news/basilea-signs-exclusive-distribution-agreement-for-zevterar-ceftobiprole-medocaril-in-the-middle-east-and-north-africa-with-hikma-pharmaceuticals-llc?type=1546938654 | access-date=7 April 2024 | archive-date=7 April 2024 | archive-url=https://web.archive.org/web/20240407013937/https://www.basilea.com/news/basilea-signs-exclusive-distribution-agreement-for-zevterar-ceftobiprole-medocaril-in-the-middle-east-and-north-africa-with-hikma-pharmaceuticals-llc?type=1546938654 | url-status=live }}</ref><ref>{{cite press release | title=Basilea announces that Health Canada approved Zevtera for the treatment of bacterial lung infections | website=Basilea | date=12 October 2015 | url=https://www.basilea.com/news/basilea-announces-that-health-canada-approved-zevterar-for-the-treatment-of-bacterial-lung-infections?type=1546938654 | access-date=7 April 2024 | archive-date=7 April 2024 | archive-url=https://web.archive.org/web/20240407013937/https://www.basilea.com/news/basilea-announces-that-health-canada-approved-zevterar-for-the-treatment-of-bacterial-lung-infections?type=1546938654 | url-status=live }}</ref> 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 ] of ] 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 '']'' (penicillin-intermediate), to penicillin-binding protein 2x in ''Streptococcus pneumoniae'' (penicillin-resistant), and to penicillin-binding protein 5 in '']''.<ref>{{cite journal | vauthors = Syed YY | title = Ceftobiprole medocaril: a review of its use in patients with hospital- or community-acquired pneumonia | journal = Drugs | volume = 74 | issue = 13 | pages = 1523–1542 | date = September 2014 | pmid = 25117196 | doi = 10.1007/s40265-014-0273-x | s2cid = 2925496 | doi-access = free }}</ref> |
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'''Ceftobiprole''' ('''Zeftera'''/'''Zevtera''') is a 5th generation<ref name="pmid20001879">{{cite journal |author=Kollef MH |title=New antimicrobial agents for methicillin-resistant Staphylococcus aureus |journal=Crit Care Resusc |volume=11 |issue=4 |pages=282–6 |year=2009 |month=December |pmid=20001879 |doi= |url=}}</ref> ] ] with activity against ], penicillin-resistant '']'', '']'', and ].<ref>{{cite journal |author=Yun HC, Ellis MW, Jorgensen JH |title=Activity of ceftobiprole against community-associated methicillin-resistant Staphylococcus aureus isolates recently recovered from US military trainees |journal= Diagnostic Microbiology and Infectious Disease|volume= 59|issue= 4|pages= 463|year=2007 |pmid=17911001 |doi=10.1016/j.diagmicrobio.2007.06.023}}</ref><ref name="2008Widmer">{{cite journal|author=Widmer A|title=Ceftobiprole: A new option for treatment of skin and soft-tissue infections due to methicillin-resistant ''Staphylococcus aureus''|journal=Clin Infect Dis|year=2008|volume=46|pages=656–8|doi=10.1086/526528|pmid=18225983|issue=5}}</ref><ref name="2008Noel">{{cite journal|author=Noel GJ, Bush K, Bagchi P, Ianus J, Strauss RS|title=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|journal=Clin Infect Dis|year=2008|volume=46|pages=647–55|doi=10.1086/526527|pmid=18225981|issue=5}}</ref> It was discovered by ]<ref name="2001Hebeisen">{{cite journal|author=Hebeisen P, Heinze-Krauss I, Angehrn P, ''et al.''|year=2001|title=In vitro and in vivo properties of Ro63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci|journal=Antimicrob Agents Chemother|volume=45|pages=825–36|doi=10.1128/AAC.45.3.825-836.2001|pmid=11181368|issue=3|pmc=90381}}</ref> and was developed by ].<ref></ref> It has been shown to be statistically non-inferior to the combination of ] and ] for the treatment of skin and soft tissue infections.{{Citation needed|date=January 2010}} |
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For adults with '']'' bloodstream infections (bacteremia), the most common side effects include anemia, nausea, low levels of potassium in the blood (hypokalemia), vomiting, diarrhea, increased levels of certain liver tests (hepatic enzymes and bilirubin), increased blood creatinine, high blood pressure, low white blood cell count (leukopenia), fever, abdominal pain, fungal infection, headache and shortness of breath (dyspnea).<ref name="FDA 20240403" /> For adults with acute bacterial skin and skin structure infections, the most common side effects include nausea, diarrhea, headache, injection site reaction, increased levels of hepatic enzymes, rash, vomiting and altered taste (dysgeusia).<ref name="FDA 20240403" /> For adults with community-acquired bacterial pneumonia, the most common side effects include nausea, increased levels of hepatic enzymes, vomiting, diarrhea, headache, rash, insomnia, abdominal pain, vein inflammation (phlebitis), high blood pressure and dizziness.<ref name="FDA 20240403" /> For children with community-acquired bacterial pneumonia, the most common side effects include vomiting, headache, increased levels of hepatic enzymes, diarrhea, infusion site reaction, vein inflammation (phlebitis) and fever.<ref name="FDA 20240403" /> |
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It has been described as a "fifth generation" cephalosporin,<ref name="pmid18225983">{{cite journal |author=Widmer AF |title=Ceftobiprole: a new option for treatment of skin and soft-tissue infections due to methicillin-resistant Staphylococcus aureus |journal=Clin. Infect. Dis. |volume=46 |issue=5 |pages=656–8 |year=2008 |month=March |pmid=18225983 |doi=10.1086/526528 |url=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}}</ref><ref name="pmid17613382">{{cite journal |author=Kosinski MA, Joseph WS |title=Update on the treatment of diabetic foot infections |journal=Clin Podiatr Med Surg |volume=24 |issue=3 |pages=383–96, vii |year=2007 |month=July |pmid=17613382 |doi=10.1016/j.cpm.2007.03.009 |url=http://journals.elsevierhealth.com/retrieve/pii/S0891-8422(07)00026-2}}</ref> though acceptance for this terminology is not universal. |
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Ceftobiprole medocaril was approved for medical use in the United States in April 2024.<ref name="FDA 20240403">{{cite press release | title=FDA Approves New Antibiotic for Three Different Uses | website=U.S. ] (FDA) | date=3 April 2024 | url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibiotic-three-different-uses | access-date=12 April 2024 | archive-date=13 April 2024 | archive-url=https://web.archive.org/web/20240413034908/https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibiotic-three-different-uses | url-status=live }} {{PD-notice}}</ref><ref>{{cite web | title=Novel Drug Approvals for 2024 | website=U.S. ] (FDA) | date=29 April 2024 | url=https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024 | access-date=30 April 2024 | archive-date=30 April 2024 | archive-url=https://web.archive.org/web/20240430031024/https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2024 | url-status=live }}</ref><ref name="Zevtera FDA snapshot">{{cite web | title=Drug Trials Snapshots: Zevtera | website=U.S. Food and Drug Administration | date=1 October 2024 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-zevtera | access-date=28 November 2024}}</ref> |
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== Medical uses == |
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In the US, ceftobiprole is ] for the treatment of adults with ''Staphylococcus aureus'' bloodstream infections (bacteremia) including those with right-sided infective endocarditis;<ref name ="Zevtera FDA label" /> adults with acute bacterial skin and skin structure infections;<ref name ="Zevtera FDA label" /> and people with community-acquired bacterial pneumonia.<ref name ="Zevtera FDA label" /><ref name="FDA 20240403" /><ref name="Zevtera FDA snapshot" /> |
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== Microbiology == |
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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'', ] and coagulase-negative ''staphylococci'', as well as against strains of methicillin-resistant ''Staphylococcus aureus'' with reduced susceptibility to linezolid, daptomycin or vancomycin.<ref>{{cite journal | vauthors = Zhanel GG, Lam A, Schweizer F, Thomson K, Walkty A, Rubinstein E, Gin AS, Hoban DJ, Noreddin AM, Karlowsky JA | title = Ceftobiprole: a review of a broad-spectrum and anti-MRSA cephalosporin | journal = American Journal of Clinical Dermatology | volume = 9 | issue = 4 | pages = 245–254 | year = 2008 | pmid = 18572975 | doi = 10.2165/00128071-200809040-00004 | s2cid = 24357533 }}</ref> Ceftobiprole has also displayed potent activity against ''Streptococcus pneumoniae'' (including penicillin-sensitive, penicillin-resistant and ceftriaxone-resistant strains) and ''Enterococcus faecalis'', but not against '']''. For Gram-negative pathogens, ceftobiprole has shown good in vitro activity against '']'' (including both ampicillin-susceptible and ampicillin-non-susceptible isolates), ''Pseudomonas aeruginosa'' and strains of ''], ] and ]'' that do not produce extended-spectrum ]. Like all other cephalosporins, ceftobiprole was inactive against strains that produce extended-spectrum β-lactamases.<ref>{{cite journal | vauthors = Farrell DJ, Flamm RK, Sader HS, Jones RN | title = Ceftobiprole activity against over 60,000 clinical bacterial pathogens isolated in Europe, Turkey, and Israel from 2005 to 2010 | journal = Antimicrobial Agents and Chemotherapy | volume = 58 | issue = 7 | pages = 3882–3888 | date = July 2014 | pmid = 24777091 | pmc = 4068590 | doi = 10.1128/AAC.02465-14 }}</ref> |
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The efficacy of ceftobiprole has been demonstrated in two large randomized, double-blind, phase III 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.<ref>{{cite journal | vauthors = Farrell DJ, Flamm RK, Sader HS, Jones RN | title = Activity of ceftobiprole against methicillin-resistant Staphylococcus aureus strains with reduced susceptibility to daptomycin, linezolid or vancomycin, and strains with defined SCCmec types | journal = International Journal of Antimicrobial Agents | volume = 43 | issue = 4 | pages = 323–327 | date = April 2014 | pmid = 24411474 | doi = 10.1016/j.ijantimicag.2013.11.005 }}</ref><ref>{{cite journal | vauthors = Nicholson SC, Welte T, File TM, Strauss RS, Michiels B, Kaul P, Balis D, Arbit D, Amsler K, Noel GJ | title = 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 | journal = International Journal of Antimicrobial Agents | volume = 39 | issue = 3 | pages = 240–246 | date = March 2012 | pmid = 22230331 | doi = 10.1016/j.ijantimicag.2011.11.005 }}</ref> |
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==Pharmacology== |
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==Pharmacology== |
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Ceftobiprole inhibits the 2a ] (pbp) of '']'' and the 2x pbp of '']''<ref name="2008Widmer"/> as well as the classic PBP-2 of MSSA. Ceftobiprole is resistant to staphylococcal ].<ref name="2001Hebeisen"/> |
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Ceftobiprole is the active moiety of the prodrug ceftobiprole medocaril and is available for intravenous treatment only. It is mainly excreted via the kidney.<ref>{{cite journal | vauthors = Awad SS, Rodriguez AH, Chuang YC, Marjanek Z, Pareigis AJ, Reis G, Scheeren TW, Sánchez AS, Zhou X, Saulay M, Engelhardt M | title = A phase 3 randomized double-blind comparison of ceftobiprole medocaril versus ceftazidime plus linezolid for the treatment of hospital-acquired pneumonia | journal = Clinical Infectious Diseases | volume = 59 | issue = 1 | pages = 51–61 | date = July 2014 | pmid = 24723282 | pmc = 4305133 | doi = 10.1093/cid/ciu219 }}</ref> |
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==Dosing== |
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Ceftobiprole cannot be given by mouth and so is given intravenously. It is not FDA approved to be used in children.<ref name="2008Noel"/> |
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== History == |
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Ceftobiprole has been approved for use in ] and ], and is under review by regulatory authorities in the ], the ], ], ] and ].<ref>, Reuters News, June 30, 2008</ref> In November 2008 the US FDA declined to approve Ceftobiprole citing data integrity concerns with two of the supporting studies,<ref>http://www.dancewithshadows.com/pillscribe/ceftobiprole-antibiotic-to-fight-tougher-bacterial-infections-fails-to-win-approval-in-us/</ref> and prompting Basilea to sue Johnson & Johnson for breach of license agreement on February 2009.<ref>{{cite press release |
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The efficacy of ceftobiprole medocaril in treating ''Staphylococcus aureus'' bloodstream infections (bacteremia) was evaluated in a randomized, controlled, double-blind, multinational, multicenter trial.<ref name="FDA 20240403" /> In the trial, researchers randomly assigned 390 participants to receive ceftobiprole medocaril (192 participants) or daptomycin plus optional aztreonam (198 participants).<ref name="FDA 20240403" /> The primary measure of efficacy for this trial was the overall success (defined as survival, symptom improvement, ''S. aureus'' bacteremia bloodstream clearance, no new ''S. aureus'' bacteremia complications and no use of other potentially effective antibiotics) at the post-treatment evaluation visit, which occurred 70 days after being randomly assigned an antibiotic.<ref name="FDA 20240403" /> A total of 69.8% of participants who received ceftobiprole medocaril achieved overall success compared to 68.7% of participants who received the comparator.<ref name="FDA 20240403" /> |
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| title = 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 |
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| publisher = Basilea Pharmaceutica |
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| date = 2009-07-02 |
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| url = http://www.basilea.com/News-and-Media/FDA-issues-ceftobiprole-Complete-Response-Letter/317 |
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| accessdate = February 2, 2010 |
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}}</ref> |
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The efficacy of ceftobiprole medocaril in treating acute bacterial skin and skin structure infections was evaluated in a randomized, controlled, double-blind, multinational trial.<ref name="FDA 20240403" /> In the trial, researchers randomly assigned 679 participants to receive either ceftobiprole medocaril (335 participants) or vancomycin plus aztreonam (344 participants).<ref name="FDA 20240403" /> The primary measure of efficacy was early clinical response 48-72 hours after start of treatment.<ref name="FDA 20240403" /> Early clinical response required a reduction of the primary skin lesion by at least 20%, survival for at least 72 hours and the absence of additional antibacterial treatment or unplanned surgery.<ref name="FDA 20240403" /> Of the participants who received ceftobiprole medocaril, 91.3% achieved an early clinical response within the necessary timeframe compared to 88.1% of participants who received the comparator.<ref name="FDA 20240403" /> |
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==Synonyms== |
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*RO0639141-000<ref name="2001Hebeisen"/> |
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*BAL9141<ref>{{cite journal|author=Jones RN, Deshpande LM, Mutnick AH, Biedenbach DJ|year=2002|title=In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci|journal=J Antimicrob Chemother|volume=50|pages=915–932|url=http://jac.oxfordjournals.org/cgi/content/full/50/6/915?ijkey=44287b37747e341869bed979dc42b8250ff5c6ce|doi=10.1093/jac/dkf249|pmid=12461013|issue=6}}</ref> |
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*Ceftobiprole medocaril |
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The efficacy of ceftobiprole medocaril in treating adults with community-acquired bacterial pneumonia was evaluated in a randomized, controlled, double-blind, multinational, multicenter trial.<ref name="FDA 20240403" /> In the trial, researchers randomly assigned 638 adults hospitalized with community-acquired bacterial pneumonia and requiring IV antibacterial treatment for at least 3 days to receive either ceftobiprole medocaril (314 participants) or ceftriaxone with optional linezolid (324 participants).<ref name="FDA 20240403" /> The primary measurement of efficacy were clinical cure rates at test-of-cure visit, which occurred 7-14 days after end-of-treatment.<ref name="FDA 20240403" /> Of the participants who received ceftobiprole medocaril, 76.4% achieved clinical cure compared to 79.3% of participants who received the comparator.<ref name="FDA 20240403" /> An additional analysis considered an earlier timepoint of clinical success at Day 3, which was 71% in participants receiving ceftobiprole medocaril and 71.1% in participants receiving the comparator.<ref name="FDA 20240403" /> |
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==References== |
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{{reflist|2}} |
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Given the similar course of community-acquired bacterial pneumonia in adults and children, the approval of ceftobiprole medocaril in children three months to less than eighteen years of age with community-acquired bacterial pneumonia was supported by evidence from the community-acquired bacterial pneumonia trial of ceftobiprole medocaril in adults and a trial in 138 children three months to less than eighteen years of age with pneumonia.<ref name="FDA 20240403" /> |
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The US ] (FDA) granted the application for ceftobiprole medocaril ], ], and ] designations for the community-acquired bacterial pneumonia, acute bacterial skin and skin structure infections, and ''Staphylococcus aureus'' bloodstream infections (bacteremia) indications.<ref name="FDA 20240403" /> The FDA granted the approval of Zevtera to Basilea Pharmaceutica International Ltd.<ref name="FDA 20240403" /> |
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== Society and culture == |
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=== Legal status === |
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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.<ref>{{cite web | title=Zevtera 500 mg powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC) | website=(emc) | date=5 April 2023 | url=https://www.medicines.org.uk/emc/product/9164/smpc | access-date=1 June 2023 | archive-date=2 June 2023 | archive-url=https://web.archive.org/web/20230602050820/https://www.medicines.org.uk/emc/product/9164/smpc | url-status=live }}</ref> |
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In February 2010, the ] of the ] 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.<ref>{{cite web | title=Zeftera (previously Zevtera) EPAR | website=] (EMA) | date=18 February 2010 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/zeftera-previously-zevtera | access-date=6 April 2024 | archive-date=1 October 2023 | archive-url=https://web.archive.org/web/20231001171110/https://www.ema.europa.eu/en/medicines/human/EPAR/zeftera-previously-zevtera | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> |
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== References == |
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{{reflist}} |
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== External links == |
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* {{ClinicalTrialsGov|NCT03138733|Ceftobiprole in the Treatment of Patients With Staphylococcus Aureus Bacteremia}} |
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* {{ClinicalTrialsGov|NCT03137173|Ceftobiprole in the Treatment of Patients With Acute Bacterial Skin and Skin Structure Infections}} |
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* {{ClinicalTrialsGov|NCT00326287|Ceftobiprole in the Treatment of Patients With Community-Acquired Pneumonia}} |
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* {{ClinicalTrialsGov|NCT03439124|Ceftobiprole in the Treatment of Pediatric Patients With Pneumonia}} |
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