Drug Information

Drug (ID: DG00220) and It's Reported Resistant Information

• Name: Oxacillin
• Synonyms: Bactocill; Ossacillina; Oxacilina; Oxacilline; Oxacillinum; Oxazocillin; Oxazocilline; Prostaphlin; Prostaphlyn; OXACILLIN SODIUM; Ossacillina [DCIT]; Sodium oxacillin; Bactocill (TN); MPI-penicillin; MPi-PC; Oxacilina (TN); Oxacilina [INN-Spanish]; Oxacillin (INN); Oxacillin [INN:BAN]; Oxacilline [INN-French]; Oxacillinum [INN-Latin]; Penicillin, Methylphenylisoxazolyl; Oxacillin, Monosodium Salt, Anhydrous; (2S,5R,6R)-3,3-dimethyl-6-[(5-methyl-3-phenyl-1,2-oxazole-4-carbonyl)amino]-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-3,3-dimethyl-6-{[(5-methyl-3-phenylisoxazol-4-yl)carbonyl]amino}-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (5-methyl-3-phenyl-4-isoxazolyl)penicillin; 2,2-dimethyl-6beta-(5-methyl-3-phenyl-1,2-oxazole-4-carboxamido)penam-3alpha-carboxylic acid; 5-Methyl-3-phenyl-4-isoxazolyl-penicillin; 6beta-(5-methyl-3-phenylisoxazol-4-yl)penicillanic 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 (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [3]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C19H19N3O5S
• IsoSMILES: CC1=C(C(=NO1)C2=CC=CC=C2)C(=O)N[C@H]3[C@@H]4N(C3=O)[C@H](C(S4)(C)C)C(=O)O
• InChI: 1S/C19H19N3O5S/c1-9-11(12(21-27-9)10-7-5-4-6-8-10)15(23)20-13-16(24)22-14(18(25)26)19(2,3)28-17(13)22/h4-8,13-14,17H,1-3H3,(H,20,23)(H,25,26)/t13-,14+,17-/m1/s1
• InChIKey: UWYHMGVUTGAWSP-JKIFEVAISA-N
• PubChem CID: 6196
• ChEBI ID: CHEBI:7809
• TTD Drug ID: D0MB8I
• VARIDT ID: DR00647
• INTEDE ID: DR2321
• DrugBank ID: DB00713

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: Mycobacterium tuberculosis H37Rv; 83332
• In Vitro Model: Escherichia coli DH10B; 316385
• In Vitro Model: Mycobacterium smegmatis PM274; 1772
• In Vitro Model: Mycobacterium smegmatis PM759; 1772
• In Vitro Model: Mycobacterium smegmatis PM791; 1772
• In Vitro Model: Mycobacterium smegmatis PM876; 1772
• In Vitro Model: Mycobacterium smegmatis PM939; 1772
• In Vitro Model: Mycobacterium smegmatis PM976; 1772
• In Vitro Model: Mycobacterium tuberculosis PM638; 1773
• In Vitro Model: Mycobacterium tuberculosis PM669; 1773
• In Vitro Model: Mycobacterium tuberculosis PM670; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay; E-strip test assay
• Mechanism Description: Mycobacteria produce Beta-lactamases and are intrinsically resistant to Beta-lactam antibiotics.The mutants M. tuberculosis PM638 (detablaC1) and M. smegmatis PM759 (detablaS1) showed an increase in susceptibility to Beta-lactam antibiotics.

Key Molecule: Penicillin binding protein PBP 2 (PBP2) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus RN4220; 1280
• In Vitro Model: Staphylococcus aureus M10/0061; 1280
• In Vitro Model: Staphylococcus aureus M10/0148; 1280
• In Vitro Model: Staphylococcus aureus WGB8404; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Disk diffusion test assay; Etest assay
• Mechanism Description: Methicillin resistance in staphylococci is mediated by penicillin binding protein 2a (PBP 2a), encoded by mecA on mobile staphylococcal cassette chromosome mec (SCCmec) elements.Whole-genome sequencing of one isolate (M10/0061) revealed a 30-kb SCCmec element encoding a class E mec complex with highly divergent blaZ-mecA-mecR1-mecI, a type 8 cassette chromosome recombinase (ccr) complex consisting of ccrA1-ccrB3, an arsenic resistance operon, and flanking direct repeats (DRs).

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Tetracycline resistance protein class A (TETA) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Corynebacterium striatum infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Corynebacterium glutamicum strain ATCC 13032; 196627
• In Vitro Model: Corynebacterium striatum strain M82B; 43770
• In Vitro Model: Escherichia coli strain DH5alphaMCR; 668369
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Macrodilution broth method assay
• Mechanism Description: The large multiresistance plasmid pTP10 was initially identified in the clinical isolate C. striatum M82B. This 51-kb R-plasmid was shown to carry the determinants for resistance to the antibiotics chloramphenicol, erythomycin, kanamycin, and tetracycline by ethidium bromide-based curing experiments. The tetracycline and oxacillin resistance region is part of a DNA segment structurally similar to the chromosome of the human pathogen Mycobacterium tuberculosis. A resistance assay in C. glutamicum demonstrated that the tetAB gene pair of pTP10 is necessary to confer resistance to the antibiotics tetracycline and oxytetracycline.

Key Molecule: Tetracycline resistance protein class A (TETA) [3]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Corynebacterium glutamicum infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Corynebacterium glutamicum strain ATCC 13032; 196627
• In Vitro Model: Corynebacterium striatum strain M82B; 43770
• In Vitro Model: Escherichia coli strain DH5alphaMCR; 668369
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Macrodilution broth method assay
• Mechanism Description: The large multiresistance plasmid pTP10 was initially identified in the clinical isolate C. striatum M82B. This 51-kb R-plasmid was shown to carry the determinants for resistance to the antibiotics chloramphenicol, erythomycin, kanamycin, and tetracycline by ethidium bromide-based curing experiments. Both resistance genes are located on mobile DNA elements that are capable of transposition into the chromosome of the non-pathogenic soil bacteriumC. glutamicum. A resistance assay in C. glutamicum demonstrated that the tetAB gene pair of pTP10 is necessary to confer resistance to the antibiotics tetracycline and oxytetracycline.

References

• Ref 1: Genetic analysis of the beta-lactamases of Mycobacterium tuberculosis and Mycobacterium smegmatis and susceptibility to beta-lactam antibiotics. Microbiology (Reading). 2005 Feb;151(Pt 2):521-532. doi: 10.1099/mic.0.27629-0.
• Ref 2: Purification and properties of the Mycobacterium smegmatis mc(2)155 beta-lactamase. FEMS Microbiol Lett. 1997 Apr 1;149(1):11-5. doi: 10.1016/s0378-1097(97)00041-4.
• Ref 3: The 51,409-bp R-plasmid pTP10 from the multiresistant clinical isolate Corynebacterium striatum M82B is composed of DNA segments initially identified in soil bacteria and in plant, animal, and human pathogens. Mol Gen Genet. 2000 Feb;263(1):1-11. doi: 10.1007/pl00008668.
• Ref 4: Detection of staphylococcal cassette chromosome mec type XI carrying highly divergent mecA, mecI, mecR1, blaZ, and ccr genes in human clinical isolates of clonal complex 130 methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2011 Aug;55(8):3765-73. doi: 10.1128/AAC.00187-11. Epub 2011 Jun 2.