Drug Information

Drug (ID: DG00078) and It's Reported Resistant Information

• Name: Cefixime
• Synonyms: CFIX; Cefixima; Cefiximum; Denvar; Necopen; Tricef; CL-284635; FK-027; FR-17027; Ofex (TN); Suprax (TN); Cefixime (JP15/USP/INN); (6R,7R)-7-({(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(carboxymethoxy)imino]acetyl}amino)-3-ethenyl-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-(carboxymethyloxyimino)acetyl]amino]-3-ethenyl-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-{[(carboxymethyl)oxy]imino}acetyl]amino}-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6r,7r)-7-[-2-(2-amino-thiazol-4-yl)-2-carboxymethoxyimino-acetylamino]-8-oxo-3-vinyl-5-thia-1-aza-b; 7beta-{(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(carboxymethoxy)imino]acetamido}-3-ethenyl-3,4-didehydrocepham-4-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 (2 diseases)
  Gonococcal infection [ICD-11: 1A72]; [7]
  Gonorrhea [ICD-11: 1A70]; [1], [2], [3]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C16H15N5O7S2
• IsoSMILES: C=CC1=C(N2[C@@H]([C@@H](C2=O)NC(=O)/C(=N\\OCC(=O)O)/C3=CSC(=N3)N)SC1)C(=O)O
• InChI: 1S/C16H15N5O7S2/c1-2-6-4-29-14-10(13(25)21(14)11(6)15(26)27)19-12(24)9(20-28-3-8(22)23)7-5-30-16(17)18-7/h2,5,10,14H,1,3-4H2,(H2,17,18)(H,19,24)(H,22,23)(H,26,27)/b20-9-/t10-,14-/m1/s1
• InChIKey: OKBVVJOGVLARMR-QSWIMTSFSA-N
• PubChem CID: 5362065
• ChEBI ID: CHEBI:472657
• TTD Drug ID: D06OVY
• VARIDT ID: DR00546
• DrugBank ID: DB00671

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.A311V
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

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

• Molecule Alteration: Missense mutation; p.T316P
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

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

• Molecule Alteration: Missense mutation; p.A311V+p.T316P
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

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

• Molecule Alteration: Missense mutation; p.T483S
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

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

• Molecule Alteration: Missense mutation; p.T483S+p.A311V+p.T316P
• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

References

• Ref 1: Reduced susceptibility to ceftriaxone in Neisseria gonorrhoeae is associated with mutations G542S, P551S and P551L in the gonococcal penicillin-binding protein 2. J Antimicrob Chemother. 2010 Aug;65(8):1615-8. doi: 10.1093/jac/dkq187. Epub 2010 May 28.
• Ref 2: High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother. 2012 Mar;56(3):1273-80. doi: 10.1128/AAC.05760-11. Epub 2011 Dec 12.
• Ref 3: Identification of amino acids conferring high-level resistance to expanded-spectrum cephalosporins in the penA gene from Neisseria gonorrhoeae strain H041. Antimicrob Agents Chemother. 2013 Jul;57(7):3029-36. doi: 10.1128/AAC.00093-13. Epub 2013 Apr 15.
• Ref 4: Structural effect of the Asp345a insertion in penicillin-binding protein 2 from penicillin-resistant strains of Neisseria gonorrhoeae. Biochemistry. 2014 Dec 9;53(48):7596-603. doi: 10.1021/bi5011317. Epub 2014 Dec 1.
• Ref 5: [The role of some individual amino acid substitutions in penicillin-binding protein (PBP2) of Neisseria gonorrhoeae in the emergence of resistance to ceftriaxone]. Mol Biol (Mosk). 2014 Nov-Dec;48(6):977-82.
• Ref 6: Molecular Characterization and Antimicrobial Resistance in Neisseria gonorrhoeae, Nunavut Region of Inuit Nunangat, Canada, 2018-2019. Emerg Infect Dis. 2021 Jun;27(6):1718-1722. doi: 10.3201/eid2706.204407.
• Ref 7: WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017-18: a retrospective observational study .Lancet Microbe. 2021 Nov;2(11):e627-e636. doi: 10.1016/S2666-5247(21)00171-3. Epub 2021 Sep 2. 10.1016/S2666-5247(21)00171-3