Drug Information

Drug (ID: DG00283) and It's Reported Resistant Information

• Name: Cefpodoxime
• Synonyms: CPDX; Cefpodoxima; Cefpodoximum; Epoxim; Cefpodoxim acid; Cefpodoxima [Spanish]; Cefpodoximum [Latin]; RU 51807; Cefpodoxime (INN); Cefpodoxime [INN:BAN]; Epoxim (TN); Vantin (TN); (6R,7R)-7-({(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(methyloxy)imino]acetyl}amino)-3-[(methyloxy)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-[[(2E)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7-{[(2-amino-1,3-thiazol-4-yl)(methoxyimino)acetyl]amino}-3-(methoxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1], [2], [3], [4], [5], [6]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Gonorrhea [ICD-11: 1A70]; [1], [2], [3]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C15H17N5O6S2
• IsoSMILES: COCC1=C(N2[C@@H]([C@@H](C2=O)NC(=O)/C(=N\\OC)/C3=CSC(=N3)N)SC1)C(=O)O
• InChI: 1S/C15H17N5O6S2/c1-25-3-6-4-27-13-9(12(22)20(13)10(6)14(23)24)18-11(21)8(19-26-2)7-5-28-15(16)17-7/h5,9,13H,3-4H2,1-2H3,(H2,16,17)(H,18,21)(H,23,24)/b19-8-/t9-,13-/m1/s1
• InChIKey: WYUSVOMTXWRGEK-HBWVYFAYSA-N
• PubChem CID: 6335986
• ChEBI ID: CHEBI:3504
• TTD Drug ID: D0W6CA
• VARIDT ID: DR00974
• INTEDE ID: DR2661
• DrugBank ID: DB01416

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-01: Infectious/parasitic diseases

Gonorrhea [ICD-11: 1A70]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Probable peptidoglycan D,D-transpeptidase PenA (PENA) [1], [2], [3]

• Molecule Alteration: Missense mutation; p.G545S
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Key Molecule: Probable peptidoglycan D,D-transpeptidase PenA (PENA) [1], [2], [3]

• Molecule Alteration: Missense mutation; p.G545S+p.I312M
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Key Molecule: Probable peptidoglycan D,D-transpeptidase PenA (PENA) [1], [2], [3]

• Molecule Alteration: Missense mutation; p.G545S+p.V316T
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

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.