Drug Information

Drug (ID: DG00681) and It's Reported Resistant Information

• Name: Pyrazinamide
• Synonyms: Pyrazinamide; pyrazinecarboxamide; 98-96-4; pyrazine-2-carboxamide; pyrazinoic acid amide; Zinamide; 2-Pyrazinecarboxamide; Aldinamide; Aldinamid; Pirazinamid; Tebrazid; Farmizina; Pirazimida; Pyrazineamide; Unipyranamide; Eprazin; Novamid; Pyrafat; pyrazine carboxylamide; 2-Carbamylpyrazine; Pyrazinecarboxylic acid amide; Pyrazinamidum; Isopas; Pirazinamide; Pyrazine carboxamide; D-50; MK 56; C5H5N3O; PZA; NCI-C01785; UNII-2KNI5N06TI; MFCD00006132; NSC 14911; T 165; Pirazinamida; Tisamid; 2KNI5N06TI; MLS000069730; Pezetamid; Piraldina; Pyrazide; CHEBI:45285; Rozide; NSC14911; Pyrazinamide (Pyrazinoic acid amide); NSC-14911; NCGC00015833-09; Pyrazinamdie; SMR000036662; Pirazinamide [DCIT]; DSSTox_CID_1215; DSSTox_RID_76014; DSSTox_GSID_21215; Pyrazinamidum [INN-Latin]; Pirazinamida [INN-Spanish]; pyramizade; Rifafour; D-50 (VAN); DRG 0124; CAS-98-96-4; CCRIS 545; Pyrazinamide (TN); Rifafour e-200; HSDB 3576; SR-01000076077; EINECS 202-717-6; BRN 0112306; pyrazinamida; Pyrizinamide; pyrazine amide; AZT + Pyrazinamide combination; Pyrazine-2-carboxylic acid amide; Pyrazinamide,(S); Pyrazinamide [USP:INN:BAN:JAN]; Prestwick_811; .alpha.-pyrazinamide; 2-pyrazine carboxamide; Spectrum_000902; Opera_ID_735; Prestwick0_000514; Prestwick1_000514; Prestwick2_000514; Prestwick3_000514; Spectrum2_001305; Spectrum3_001046; Spectrum4_001186; Spectrum5_001026; Lopac-P-7136; CHEMBL614; P 7136; WLN: T6N DNJ BVZ; pyrazine-2-carboximidic acid; Lopac0_001011; SCHEMBL24102; BSPBio_000467; BSPBio_002572; KBioGR_001851; KBioSS_001382; 5-25-04-00178 (Beilstein Handbook Reference); MLS002222347; BIDD:GT0228; DivK1c_000241; SPECTRUM1500518; SPBio_001369; SPBio_002388; BPBio1_000515; GTPL7287; ZINC2005; DTXSID9021215; HMS500M03; KBio1_000241; KBio2_001382; KBio2_003950; KBio2_006518; KBio3_001792; Pyrazinamide (JP17/USP/INN); NINDS_000241; BDBM228814; HMS1569H09; HMS1920N08; HMS2092E09; HMS2096H09; HMS2235G17; HMS3259O04; HMS3263K03; HMS3371G09; HMS3655A10; HMS3713H09; KUC109577N; Pharmakon1600-01500518; ACT01761; AMY14180; BCP30257; HY-B0271; KSC-27-052E; Pyrazine-[d3]-carboxamide-[15N]; Tox21_110237; Tox21_202059; Tox21_302771; Tox21_501011; CCG-39243; NSC757304; s1762; STK801661; AKOS000120280; Tox21_110237_1; DB00339; LP01011; MCULE-6846697749; NC00534; NSC-757304; Pyrazinecarboxamide, analytical standard; SDCCGSBI-0050984.P005; IDI1_000241; NCGC00015833-01; NCGC00015833-02; NCGC00015833-03; NCGC00015833-04; NCGC00015833-05; NCGC00015833-06; NCGC00015833-07; NCGC00015833-08; NCGC00015833-10; NCGC00015833-11; NCGC00015833-12; NCGC00015833-15; NCGC00015833-16; NCGC00015833-25; NCGC00090695-01; NCGC00090695-03; NCGC00090695-04; NCGC00090695-05; NCGC00090695-06; NCGC00090695-07; NCGC00256336-01; NCGC00259608-01; NCGC00261696-01; Pyrazinoic acid amide; pyrazinamide; PZA; CAS- 98-96-4; SY013550; TS-01626; SBI-0050984.P004; DB-002866; AB00052083; B2122; BB 0253141; EU-0101011; FT-0659757; P0633; SW196945-3; C01956; D00144; D70481; J10111; 1,2-dihydro-1,2,4-triazol-3-one;Pyrazinamide; AB00052083-16; AB00052083_17; AB00052083_18; A845937; AC-907/25014068; Q417571; SR-01000076077-1; SR-01000076077-4; SR-01000076077-6; W-100059; Z33546644; Pyrazinamide, British Pharmacopoeia (BP) Reference Standard; Pyrazinamide, European Pharmacopoeia (EP) Reference Standard; 2-Carbamylpyrazine ;Aldinamid ;Aldinamide; Pyrazinoic acid amide; Pyrazinamide, United States Pharmacopeia (USP) Reference Standard; Pyrazinamide, Pharmaceutical Secondary Standard; Certified Reference Material
• Indication:
  In total 1 Indication(s)
  Mycobacterium infection [ICD-11: 1B10-1B21]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Bifidobacterium [ICD-11: XN33F]; [2]
  Tuberculosis [ICD-11: 1B10]; [3]
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Mycobacterial diseases [ICD-11: 1B2Z ]; [1]
  Tuberculous sclerokeratitis [ICD-11: 1B12]; [4]
• Target: Bacterial Fatty acid synthetase I (Bact inhA); INHA_MYCTU; [1]
• Formula: C5H5N3O
• IsoSMILES: C1=CN=C(C=N1)C(=O)N
• InChI: 1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)
• InChIKey: IPEHBUMCGVEMRF-UHFFFAOYSA-N
• PubChem CID: 1046
• ChEBI ID: CHEBI:45285
• TTD Drug ID: D0XF8W
• INTEDE ID: DR1372
• DrugBank ID: DB00339

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Tuberculosis [ICD-11: 1B10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Pyrazinamidase/nicotinamidase (PncA) [3]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Mutation; Q859H/K
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: GeneSeq assay; Bioinformatics assay
• Mechanism Description: Out of total 112 mycobacterial positive cultures, five?M. bovis?were isolated and underwent WGS. All sequenced strains belonged to?Mycobacterium tuberculosis var bovis, spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA?and?rpsA), isoniazid (KatG?and?ahpC), ethambutol (embB,?embC,?embR?and?ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA?and?gyrB). Rifampin (rpoB?and?rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system.

Key Molecule: Small ribosomal subunit protein uS2 (RPSA) [3]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Mutation; rpoB gene
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: GeneSeq assay; Bioinformatics assay
• Mechanism Description: Out of total 112 mycobacterial positive cultures, five?M. bovis?were isolated and underwent WGS. All sequenced strains belonged to?Mycobacterium tuberculosis var bovis, spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA?and?rpsA), isoniazid (KatG?and?ahpC), ethambutol (embB,?embC,?embR?and?ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA?and?gyrB). Rifampin (rpoB?and?rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system.

ICD-X: Extension Codes

Bifidobacterium [ICD-11: XN33F]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Pyrazinamidase [2]

• Resistant Disease: bifidobacterium adolescentis infection [ICD-11: XN33F]
• Molecule Alteration: Missense mutation; Q24K+L28M+R30E+A92K
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Bifidobacterial strains; 1763
• Experiment for Molecule Alteration: PCR; Catalase foam assay; Catalase gel assay
• Experiment for Drug Resistance: Growth curve assay; Spot assay; Anti-tubercular drug uptake and surface assay; Adaptability assay; FE-SEM assay; MIC assay; Particle size assay
• Mechanism Description: The current study aims to understand the resistance of Bifidobacterium adolescentis to different anti-tubercular drugs (first-line oral tuberculosis drugs). The bacteria were grown with anti-tubercular drugs such as isoniazid, pyrazinamide, and streptomycin to better understand the resistance phenomena. It was found that even at tenfold higher concentrations, growth rates remained unchanged. In addition, a small number of bacteria were found to aggregate strongly, a property that protects against the toxicity of the drug. Further FE-SEM (Field Emission Scanning Electron Microscopy) analysis revealed that some bacteria became excessively long, elongated, and protruded on the surface. Size scattering analysis confirmed the presence of bifidobacteria in the size range of 1.0-100 um. After whole genome sequence analysis, certain mutations were found in the relevant gene. In vitro, foam formation and growth in the presence of H2O2 and HPLC (High Performance Liquid Chromatography) studies provide additional evidence for the presence of catalase. According to RAST (Rapid Annotation Using Subsystems Technology) annotation and CARD (Comprehensive Antibiotic Resistance Database analysis), there were not many components in the genome that were resistant to antibiotics. Whole genome sequence (WGS) analysis does not show the presence of bacteriocins and antibiotic resistance genes, but few hypothetical proteins were observed. 3D structure and docking studies suggest their interaction with specific ligands.

References

• Ref 1: Pyrazinamide resistance in Mycobacterium tuberculosis fails to bite .Pathog Dis. 2015 Aug;73(6):ftv037. doi: 10.1093/femspd/ftv037. Epub 2015 May 19. 10.1093/femspd/ftv037
• Ref 2: Bifidobacterium adolescentis is resistant to pyrazinamide, isoniazid, and streptomycin. Sci Rep. 2024 Nov 28;14(1):29562.
• Ref 3: Genetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing. BMC Genomics. 2024 Nov 1;25(1):1024.
• Ref 4: Tuberculous Scleritis and Multidrug ResistanceOcul Immunol Inflamm. 2021 Jan 8:1-10. doi: 10.1080/09273948.2020.1853176. Online ahead of print.