Drug Information

Drug (ID: DG00143) and It's Reported Resistant Information

• Name: Cefotetan
• Synonyms: Cefotetanum; Apatef (TN); Cefotan (TN); Cefotetan (JP15/USP/INN); (6R,7S)-7-(4-(carbamoylcarboxymethylene)-1,3-dithiethane-2-carboxamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid; (6R,7S)-7-({[4-(2-amino-1-carboxy-2-oxoethylidene)-1,3-dithietan-2-yl]carbonyl}amino)-7-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7S)-7-[[4-(1-amino-3-hydroxy-1,3-dioxopropan-2-ylidene)-1,3-dithietane-2-carbonyl]amino]-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7beta-({[4-(2-amino-1-carboxy-2-oxoethylidene)-1,3-dithietan-2-yl]carbonyl}amino)-7alpha-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-3,4-didehydrocepham-4-carboxylic acid
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1], [2]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1], [2]
  Non-tuberculous mycobacteria infection [ICD-11: 1B21]; [3]
  Tissue pyogenic bacterial infection [ICD-11: 1B7Y]; [4]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C17H17N7O8S4
• IsoSMILES: CN1C(=NN=N1)SCC2=C(N3[C@@H]([C@@](C3=O)(NC(=O)C4SC(=C(C(=O)N)C(=O)O)S4)OC)SC2)C(=O)O
• InChI: 1S/C17H17N7O8S4/c1-23-16(20-21-22-23)34-4-5-3-33-15-17(32-2,14(31)24(15)7(5)11(29)30)19-9(26)13-35-12(36-13)6(8(18)25)10(27)28/h13,15H,3-4H2,1-2H3,(H2,18,25)(H,19,26)(H,27,28)(H,29,30)/t13 ,15-,17+/m1/s1
• InChIKey: SRZNHPXWXCNNDU-RHBCBLIFSA-N
• PubChem CID: 53025
• ChEBI ID: CHEBI:3499
• TTD Drug ID: D0AP9T
• VARIDT ID: DR01386
• DrugBank ID: DB01330

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [1], [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain DH5a; 668369
• In Vitro Model: Klebsiella pneumoniae strain HEL-1; 573
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: The phenotype of Klebsiella pneumoniae HEL-1 indicates a plasmidic cephamycinase gene (blaCMY-2),which is responsible for cephamycin resistance.

Tissue pyogenic bacterial infection [ICD-11: 1B7Y]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to ampicillin resistance in the staphylococcus infection.

References

• Ref 1: Identifying novel Beta-lactamase substrate activity through in silico prediction of antimicrobial resistance. Microb Genom. 2021 Jan;7(1):mgen000500. doi: 10.1099/mgen.0.000500.
• Ref 2: Characterization of the plasmidic beta-lactamase CMY-2, which is responsible for cephamycin resistance. Antimicrob Agents Chemother. 1996 Jan;40(1):221-4. doi: 10.1128/AAC.40.1.221.
• Ref 3: Investigation and analysis of the characteristics and drug sensitivity of bacteria in skin ulcer infections .Chin J Traumatol. 2017 Aug;20(4):194-197. doi: 10.1016/j.cjtee.2016.09.005. Epub 2017 May 24. 10.1016/j.cjtee.2016.09.005
• Ref 4: Pathogen characteristics reveal novel antibacterial approaches for interstitial lung disease .Pulm Pharmacol Ther. 2014 Dec;29(2):250-4. doi: 10.1016/j.pupt.2014.03.005. Epub 2014 Apr 1. 10.1016/j.pupt.2014.03.005