Drug Information

Drug (ID: DG00146) and It's Reported Resistant Information

• Name: Vancomycin
• Synonyms: Vancomycin (oral, MRSA), AuricX; Vancomycin (oral/pill, MSRA); Vancomycin (oral/pill, MSRA), AuricX/SRI International
• Indication:
  In total 2 Indication(s)
  Anaerobic bacterial infection [ICD-11: 1A00-1A09]; Approved; [1]
  Infectious meningitis [ICD-11: 1D01]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2]
  Sclerosing cholangitis [ICD-11: DB96]; [3]
  Staphylococcus meningitis [ICD-11: 1B54]; [4]
• Formula: C66H75Cl2N9O24
• IsoSMILES: C[C@H]1[C@H]([C@@](C[C@@H](O1)O[C@@H]2[C@H]([C@@H]([C@H](O[C@H]2OC3=C4C=C5C=C3OC6=C(C=C(C=C6)[C@H]([C@H](C(=O)N[C@H](C(=O)N[C@H]5C(=O)N[C@@H]7C8=CC(=C(C=C8)O)C9=C(C=C(C=C9O)O)[C@H](NC(=O)[C@H]([C@@H](C1=CC(=C(O4)C=C1)Cl)O)NC7=O)C(=O)O)CC(=O)N)NC(=O)[C@@H](CC(C)C)NC)O)Cl)CO)O)O)(C)N)O
• InChI: 1S/C66H75Cl2N9O24/c1-23(2)12-34(71-5)58(88)76-49-51(83)26-7-10-38(32(67)14-26)97-40-16-28-17-41(55(40)101-65-56(54(86)53(85)42(22-78)99-65)100-44-21-66(4,70)57(87)24(3)96-44)98-39-11-8-27(15-33(39)68)52(84)50-63(93)75-48(64(94)95)31-18-29(79)19-37(81)45(31)30-13-25(6-9-36(30)80)46(60(90)77-50)74-61(91)47(28)73-59(89)35(20-43(69)82)72-62(49)92/h6-11,13-19,23-24,34-35,42,44,46-54,56-57,65,71,78-81,83-87H,12,20-22,70H2,1-5H3,(H2,69,82)(H,72,92)(H,73,89)(H,74,91)(H,75,93)(H,76,88)(H,77,90)(H,94,95)/t24-,34+,35-,42+,44-,46+,47+,48-,49+,50-,51+,52+,53+,54-,56+,57+,65-,66-/m0/s1
• InChIKey: MYPYJXKWCTUITO-LYRMYLQWSA-N
• PubChem CID: 14969
• ChEBI ID: CHEBI:28001
• TTD Drug ID: D0B1IV
• INTEDE ID: DR2170
• DrugBank ID: DB00512

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

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

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA-directed RNA polymerase subunit beta' (RPOC) [1]

• Molecule Alteration: Missense mutation; p.D244Y
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Clostridioides difficile ATCC 43255; 499175
• In Vitro Model: Clostridioides difficile NB95009; 1496
• In Vitro Model: Clostridioides difficile NB95026; 1496
• In Vitro Model: Clostridioides difficile NB95031; 1496
• In Vitro Model: Clostridioides difficile NB95047; 1496
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: NB95026-JAL0865 had a single mutation encoding a D244Y substitution in the RNA polymerase subunit Beta.Reduced susceptibility to fidaxomicin and vancomycin was associated with mutations mediating target modifications (RNA polymerase and cell wall, respectively), as well as with mutations that may contribute to reduced susceptibility via other mechanisms.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Putative ABC transporter ATP-binding component (OTRC) [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 BL21 (DE3); 469008
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli ET12567 (pUZ8002); 562
• In Vitro Model: Streptomyces rimosus M4018; 1927
• In Vitro Model: Streptomyces rimosus SR16; 1927
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: OtrC is a multidrug resistance protein based on an ATP hydrolysis-dependent active efflux mechanism.OtrC is a multidrug resistance protein based on an ATP hydrolysis-dependent active efflux mechanism.

Staphylococcus meningitis [ICD-11: 1B54]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Phosphatidylglycerol lysyltransferase (MPREF) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• Experiment for Molecule Alteration: TLC and Western blotting analysis
• Experiment for Drug Resistance: Epsilometer test (E test) assay
• Mechanism Description: MprF does not only synthesize Lys-PG but also accomplishes translocation of Lys-PG from the inner to the outer surface of the membrane. Lys-PG mediates CAMP resistance by repulsing the cationic peptides from the outer surface of the membrane.

References

• Ref 1: In vitro selection, via serial passage, of Clostridium difficile mutants with reduced susceptibility to fidaxomicin or vancomycin. J Antimicrob Chemother. 2014 Jan;69(1):41-4. doi: 10.1093/jac/dkt302. Epub 2013 Jul 25.
• Ref 2: Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus. BMC Biotechnol. 2012 Aug 20;12:52. doi: 10.1186/1472-6750-12-52.
• Ref 3: Treatment options for other hepatic malignancies .Liver Transpl. 2000 Nov;6(6 Suppl 2):S23-9. doi: 10.1053/jlts.2000.18687. 10.1053/jlts.2000.18687
• Ref 4: The bacterial defensin resistance protein MprF consists of separable domains for lipid lysinylation and antimicrobial peptide repulsion. PLoS Pathog. 2009 Nov;5(11):e1000660. doi: 10.1371/journal.ppat.1000660. Epub 2009 Nov 13.