Drug Information

Drug (ID: DG00207) and It's Reported Resistant Information

• Name: Cefotiam
• Synonyms: Aspil; CTM; Cefotiamum; Ceradolan; Haloapor; CEFOTIAM HYDROCHLORIDE; CGP 14221E; Abbott-48999; Aspil (TN); Cefotiam (INN); Cefotiam [INN:BAN]; Cefotiamum [INN-Latin]; SCE-963; CGP-14221-E; (6R,7R)-7-[2-(2-Amino-thiazol-4-yl)-acetylamino]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-3-[[1-(2-dimethylaminoethyl)tetrazol-5-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}-3-[({1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-yl}sulfanyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-{[(2-amino-1,3-thiazol-4-yl)acetyl]amino}-3-[({1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-yl}thio)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7b-[2-(aminothiazol-4-yl)acetamido]-3-[[[1-(2-dimethylaminoethyl)-1h-tetrazol-5-yl]thio]methyl]ceph-3-em-4-carboxylic acid; 7beta-(2-amino-1,3-thiazol-4-yl)acetamido-3-[({1-[2-(dimethylamino)ethyl]-1H-tetrazol-5-yl}sulfanyl)methyl]-3,4-didehydrocepham-4-carboxylic acid
• Indication:
  In total 1 Indication(s)
  Respiratory infection [ICD-11: CA07-CA4Z]; 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 3 (Bact mrcA); FTSI_ECOLI; [1]
• Formula: C18H23N9O4S3
• IsoSMILES: CN(C)CCN1C(=NN=N1)SCC2=C(N3[C@@H]([C@@H](C3=O)NC(=O)CC4=CSC(=N4)N)SC2)C(=O)O
• InChI: 1S/C18H23N9O4S3/c1-25(2)3-4-26-18(22-23-24-26)34-7-9-6-32-15-12(14(29)27(15)13(9)16(30)31)21-11(28)5-10-8-33-17(19)20-10/h8,12,15H,3-7H2,1-2H3,(H2,19,20)(H,21,28)(H,30,31)/t12-,15-/m1/s1
• InChIKey: QYQDKDWGWDOFFU-IUODEOHRSA-N
• PubChem CID: 43708
• ChEBI ID: CHEBI:355510
• TTD Drug ID: D0K3DQ
• VARIDT ID: DR01194
• DrugBank ID: DB00229

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.