Drug Information

Drug (ID: DG00156) and It's Reported Resistant Information

• Name: Ceftobiprole
• Synonyms: BAL 9141; BAL 9141-000; BAL-9141; Ro 63-9141; Ro-63-9141; Ro-63-9141/000; (6R,7R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-ylidene)-2-nitrosoacetyl]amino]-8-oxo-3-[(E)-[2-oxo-1-[(3R)-pyrrolidin-3-yl]pyrrolidin-3-ylidene]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• Indication:
  In total 2 Indication(s)
  Pneumonia [ICD-11: CA40]; Phase 3; [1], [2], [3], [4], [5], [6]
  Skin and skin-structure infection [ICD-11: 1F28-1G0Z]; Phase 3; [1], [2], [3], [4], [5], [6]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Pneumonia [ICD-11: CA40]; [1], [2], [3]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C20H22N8O6S2
• IsoSMILES: C1CNC[C@@H]1N2CC/C(=C\\C3=C(N4[C@@H]([C@@H](C4=O)NC(=O)/C(=N\\O)/C5=NSC(=N5)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
• InChIKey: VOAZJEPQLGBXGO-SDAWRPRTSA-N
• PubChem CID: 135413542
• ChEBI ID: CHEBI:140407
• TTD Drug ID: D0CI9T
• DrugBank ID: DB04918

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]

• Molecule Alteration: Missense mutation; p.I371T
• Resistant Disease: Community-acquired pneumonia [ICD-11: CA40.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.

Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]

• Molecule Alteration: Missense mutation; p.R384G
• Resistant Disease: Community-acquired pneumonia [ICD-11: CA40.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.

Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]

• Molecule Alteration: Missense mutation; p.M400T
• Resistant Disease: Community-acquired pneumonia [ICD-11: CA40.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.

Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]

• Molecule Alteration: Missense mutation; p.M339F
• Resistant Disease: Community-acquired pneumonia [ICD-11: CA40.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.

Key Molecule: Penicillin-binding protein 2X (PBP2X) [1], [2], [3]

• Molecule Alteration: Missense mutation; STMK motif p.M>F
• Resistant Disease: Community-acquired pneumonia [ICD-11: CA40.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.

Key Molecule: Penicillin-binding protein 1A (PBP1A) [1], [2], [3]

• Molecule Alteration: Missense mutation; STMK motif p.T >A +SRNVP motif p.P >T
• Resistant Disease: Community-acquired pneumonia [ICD-11: CA40.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.

Key Molecule: Penicillin-binding protein 2B (PBP2B) [1], [2], [3]

• Molecule Alteration: Missense mutation; p.KTGTA motif p.A >G
• Resistant Disease: Community-acquired pneumonia [ICD-11: CA40.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.

References

• Ref 1: Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2006 Nov;50(11):3638-45. doi: 10.1128/AAC.00626-06. Epub 2006 Aug 28.
• Ref 2: Resistance to Beta-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins. Antibiotics (Basel). 2016 Sep 28;5(4):35. doi: 10.3390/antibiotics5040035.
• Ref 3: Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. J Biol Chem. 2009 Jan 9;284(2):1202-12. doi: 10.1074/jbc.M805761200. Epub 2008 Nov 4.
• Ref 4: In Vitro selection of Neisseria gonorrhoeae mutants with elevated MIC values and increased resistance to cephalosporins. Antimicrob Agents Chemother. 2014 Nov;58(11):6986-9. doi: 10.1128/AAC.03082-14. Epub 2014 Sep 8.
• Ref 5: Effect of Variants of Penicillin-Binding Protein 2 on Cephalosporin and Carbapenem Susceptibilities in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2015 Aug;59(8):5003-6. doi: 10.1128/AAC.05143-14. Epub 2015 May 18.
• Ref 6: Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro. Antimicrob Agents Chemother. 2016 Mar 25;60(4):2043-51. doi: 10.1128/AAC.00149-15. Print 2016 Apr.