Drug Information

Drug (ID: DG00129) and It's Reported Resistant Information

• Name: Cefazolin
• Synonyms: CEZ; Cefamezin; Cefamezine; Cefazolina; Cefazoline; Cefazolinum; Cephamezine; Cephazolidin; Cephazolin; Cephazoline; Elzogram; Cephazolin Sodium; Ancef (TN); Cefacidal (TN); Cefamezin (TN); Cefazolin (USP); Cefazolin [USAN:INN]; Cefazolin(usp); Cefazolina [INN-Spanish]; Cefazoline [INN-French]; Cefazolinum [INN-Latin]; Cefrina (TN); Elzogram (TN); Faxilen (TN); Gramaxin (TN); Kefazol (TN); Kefol (TN); Kefzol (TN); Kefzolan (TN); Kezolin (TN); Novaporin (TN); Zolicef (TN); (6R, 7R)-3-[[(5-Methyl-1,3,4-thiadiazol-2-yl)thio]methyl]-8-oxo-7-[[1H-tetrazol-1-yl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-3-(((5-Methyl-1,3,4-thiadiazol-2-yl)thio)methyl)-8-oxo-7-(2-(1H-tetrazol-1-yl)acetamido)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid; (6R,7R)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-7-[[2-(tetrazol-1-yl)acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-8-oxo-7-[(1H-tetrazol-1-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-3-{[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl}-8-oxo-7-[(1H-tetrazol-1-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R-trans)-3-(((5-Methyl-1,3,4-thiadiazol-2-yl)thio)methyl)-8-oxo-7-(((1H-tetrazol-1-yl)acetyl)-amino)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid; 3-{[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]methyl}-7beta-[(1H-tetrazol-1-ylacetyl)amino]-3,4-didehydrocepham-4-carboxylic acid; 7-(1-(1H-)-Tetrazolylacetamido)-3-(2-(5-methyl-1,3,4-thiadiazolyl)thiomethyl)delta3-cephem-4-carboxylic acid
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1], [2], [3]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (4 diseases)
  Non-tuberculous mycobacteria infection [ICD-11: 1B21]; [4]
  Pancreatitis [ICD-11: DC31]; [5]
  Pneumonia [ICD-11: CA40]; [6]
  Tissue pyogenic bacterial infection [ICD-11: 1B7Y]; [7]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1], [2], [3]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C14H14N8O4S3
• IsoSMILES: CC1=NN=C(S1)SCC2=C(N3[C@@H]([C@@H](C3=O)NC(=O)CN4C=NN=N4)SC2)C(=O)O
• InChI: 1S/C14H14N8O4S3/c1-6-17-18-14(29-6)28-4-7-3-27-12-9(11(24)22(12)10(7)13(25)26)16-8(23)2-21-5-15-19-20-21/h5,9,12H,2-4H2,1H3,(H,16,23)(H,25,26)/t9-,12-/m1/s1
• InChIKey: MLYYVTUWGNIJIB-BXKDBHETSA-N
• PubChem CID: 33255
• ChEBI ID: CHEBI:474053
• TTD Drug ID: D09KDN
• VARIDT ID: DR00577
• INTEDE ID: DR2503
• DrugBank ID: DB01327

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

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Outer membrane porin C (OMPC) [1], [2], [3]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli 1422; 562
• In Vitro Model: Escherichia coli 1437; 562
• In Vitro Model: Escherichia coli B1343; 562
• In Vitro Model: Escherichia coli B1350; 562
• In Vitro Model: Escherichia coli B1421; 562
• In Vitro Model: Escherichia coli pop1010; 562
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Permeability of the outer membrane to lowmolecular-weight hydrophilic molecules is due to the presence of porin protein molecules such as OmpF and OmpC, which form pores in the outer membrane that allow small molecules to diffuse rapidly into the periplasmic space.The case of cephaloridine and cefazolin is remarkable because mutants lacking the OmpF or the OmpC proteins individually were as susceptible to cefaloridine and cefazolin as was the wild type, but mutants lacking both proteins were resistant to these Beta-lactams.

Non-tuberculous mycobacteria infection [ICD-11: 1B21]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [8]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Cutaneous bacterial infection [ICD-11: 1B21.4]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Acinetobacter baumannii isolates; 470
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Broth microdilution method assay; Agar dilution method assay
• Mechanism Description: The isolate was resistant to antibiotics other than ampicillin-sulbactam and colistin, suggesting drug resistance due to carbapenemase production by OXA-23.carbapenem resistance in the isolated carbapenem-resistant A. baumannii strain was at least partially conferred by bla OXA-23-like carbapenemase.

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) [7]

• 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 cefazolin resistance in the staphylococcus infection.

References

• Ref 1: Antibiotic stress, genetic response and altered permeability of E. coli. PLoS One. 2007 Apr 11;2(4):e365. doi: 10.1371/journal.pone.0000365.
• Ref 2: Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance. Clin Microbiol Rev. 2012 Oct;25(4):661-81. doi: 10.1128/CMR.00043-12.
• Ref 3: Role of porin proteins OmpF and OmpC in the permeation of beta-lactams. Antimicrob Agents Chemother. 1982 Dec;22(6):942-8. doi: 10.1128/AAC.22.6.942.
• Ref 4: 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 5: Infectious Complications in Severe Acute Pancreatitis: Pathogens, Drug Resistance, and Status of Nosocomial Infection in a University-Affiliated Teaching HospitalDig Dis Sci. 2020 Jul;65(7):2079-2088. doi: 10.1007/s10620-019-05924-9. Epub 2019 Nov 5.
• Ref 6: Analysis of clinical distribution and drug resistance of klebsiella pneumoniae pulmonary infection in patients with hypertensive intra cerebral hemorrhage after minimally invasive surgeryPak J Med Sci. 2022 Jan-Feb;38(1):237-242. doi: 10.12669/pjms.38.1.4439.
• Ref 7: 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
• Ref 8: Daptomycin .J Antimicrob Chemother. 2018 Jan 1;73(1):1-11. doi: 10.1093/jac/dkx349. 10.1093/jac/dkx349