Drug General Information
Drug ID D0XF8W
Drug Name Pyrazinamide
Synonyms Aldinamid; Aldinamide; Braccopiral; Corsazinmid; Dipimide; Eprazin; Farmizina; Isopas; Lynamide; Novamid; Pezetamid; Pharozinamide; Piraldina; Pirazimida; Pirazinamid; Pirazinamida; Pirazinamide; Prazina; Pyrafat; Pyramide; Pyrazide; Pyrazinamdie; Pyrazinamidum; Pyrazineamide; Pyrazinecarboxamide; Rozide; Tebrazid; Tebrazio; Tisamid; Unipyranamide; Zinamide; Zinastat; P ezetamid; Pirazinamide [DCIT]; Pyrazine carboxamide; Pyrazine carboxylamide; Pyrazinecarboxylic acid amide; Pyrazinoic acid am ide; Pyrazinoic acid amide; DRG 0124; MK 56; P 7136; Pyrazinamide BP 2000; T 165; AZT + Pyrazinamide combination; D-50; Pirazinamida [INN-Spanish]; Pms-Pyrazinamide; Pyrazinamide (TN); Pyrazinamidum [INN-Latin]; D-50 (VAN); Pyrazinamide [INN:BAN:JAN]; Pyrazine-2-carboxamide; Pyrazinamide (JP15/USP/INN); Pyrazinoic acid amide, Pezetamid, Pyrafat, Zinamide, Tebrazid, Pyrafat, Pyrazinamide; 2-Carbamylpyrazine; 2-carbamyl pyrazine
Drug Type Small molecular drug
Therapeutic Class Antitubercular Agents
Structure D0XF8W
Drug Resistance Mutations
Target Name Bacterial Pyrazinamidase (pncA) Target Info
Gene Name pncA
Uniprot ID PNCA_MYCTU
Species Mycobacterium tuberculosis
Reference Sequence MRALIIVDVQNDFCEGGSLAVTGGAALARAISDYLAEAADYHHVVATKDFHIDPGDHFSG
TPDYSSSWPPHCVSGTPGADFHPSLDTSAIEAVFYKGAYTGAYSGFEGVDENGTPLLNWL
RQRGVDEVDVVGIATDHCVRQTAEDAVRNGLATRVLVDLTAGVSADTTVAALEEMRTASV
ELVCSS [Mycobacterium tuberculosis]
Targeted Disease Tuberculosis
Drug Resistance Mutations
Mutation info Frameshift: Plus 130 [1], [2], [3]
Mutation info Missense: I90S [4], [5], [6]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Frameshift: Plus 54 [2], [3], [7]
Mutation info Frameshift: Plus 96 [2], [7], [8]
Mutation info Missense: P69R [3], [6], [9]
Mutation info Missense: F58L [6], [8], [10]
Mutation info Missense: Q10P [6], [8], [11]
Mutation info Missense: A171P [12], [6]
Mutation info Frameshift: Plus 102 [1], [2]
Mutation info Frameshift: Plus 114 [1], [13]
Mutation info Frameshift: Plus 140 [1], [13]
Mutation info Missense: V155G [1], [6]
Mutation info Missense: A102T [14], [6]
Mutation info Missense: A102V [14], [6]
Mutation info Missense: A161P [14], [6]
Mutation info Missense: D49V [14], [6]
Mutation info Missense: D8Y [14], [6]
Mutation info Missense: I133T [14], [6]
Mutation info Missense: K96E [14], [6]
Mutation info Missense: L116R [14], [6]
Mutation info Missense: Q10K [14], [6]
Mutation info Missense: R154G [14], [6]
Mutation info Missense: S66P [14], [6]
Mutation info Missense: T160P [14], [6]
Mutation info Missense: T47S [14], [6]
Mutation info Missense: V125D [14], [6]
Mutation info Missense: A171T [15], [6]
Mutation info Missense: A171V [15], [6]
Mutation info Missense: D136H [15], [6]
Mutation info Missense: H51Y [15], [6]
Mutation info Missense: L172A [15], [6]
Mutation info Missense: L85R [15], [6]
Mutation info Missense: P62H [15], [6]
Mutation info Missense: Y103H [15], [6]
Mutation info Missense: A134V [10], [6]
Mutation info Missense: V7F [10], [6]
Mutation info Missense: A46E [13], [6]
Mutation info Missense: A46V [13], [6]
Mutation info Missense: C138S [13], [6]
Mutation info Missense: D53A [13], [6]
Mutation info Missense: G97S [13], [6]
Mutation info Missense: H71E [13], [6]
Mutation info Missense: H82R [13], [6]
Mutation info Frameshift: Plus 100 [13], [9]
Mutation info Frameshift: Plus 149 [13], [3]
Mutation info Missense: Q10R [13], [6]
Mutation info Missense: T168N [13], [6]
Mutation info Missense: V139M [13], [6]
Mutation info Missense: N118T [9], [6]
Mutation info Frameshift: Plus 123 [9], [2]
Mutation info Frameshift: Plus 134 [9], [16]
Mutation info Frameshift: Plus 1 [9], [3]
Mutation info Frameshift: Plus 24 [9], [16]
Mutation info Missense: T47P [9], [6]
Mutation info Missense: Y41H [9], [6]
Mutation info Missense: T76I [17], [6]
Mutation info Missense: G78D [11], [6]
Mutation info Missense: T135P [11], [6]
Mutation info Missense: V139L [11], [6]
Mutation info Nonsense: Y103 STOP [14], [11]
Mutation info Missense: A146T [2], [6]
Mutation info Missense: C14Y [2], [6]
Mutation info Missense: D136N [2], [6]
Mutation info Missense: D136Y [2], [6]
Mutation info Missense: D49A [2], [6]
Mutation info Missense: G23V [2], [6]
Mutation info Missense: K96Q [2], [6]
Mutation info Missense: L159R [2], [6]
Mutation info Missense: L4W [2], [6]
Mutation info Frameshift: Plus 127 [2], [18]
Mutation Frequency 1 out of 48 patients
Mutation info Missense: V180F [2], [6]
Mutation info Missense: V45G [2], [6]
Mutation info Missense: V7D [2], [6]
Mutation info Missense: V9G [2], [6]
Mutation info Missense: W68G [2], [6]
Mutation info Missense: W68R [2], [6]
Mutation info Missense: W68S [2], [6]
Mutation info Missense: Y103S [2], [6]
Mutation info Missense: A3E [19], [6]
Mutation info Missense: C72W [19], [6]
Mutation info Missense: H51Q [19], [6]
Mutation info Missense: M175V [19], [6]
Mutation info Missense: R148S [17], [19]
Mutation info Missense: C138Y [7], [6]
Mutation info Missense: Q141P [7], [6]
Mutation info Missense: A26G [3], [6]
Mutation info Missense: C14R [3], [6]
Mutation info Missense: C72R [3], [6]
Mutation info Missense: D12A [3], [6]
Mutation info Missense: D12N [3], [6]
Mutation info Missense: G132S [3], [6]
Mutation info Missense: H137P [3], [6]
Mutation info Missense: I5S [3], [6]
Mutation info Missense: K96N [3], [6]
Mutation info Missense: L85P [3], [6]
Mutation info Missense: T142K [3], [6]
Mutation info Missense: T142M [3], [6]
Mutation info Frameshift: Plus 132 [16], [8]
Mutation info Missense: G17D [8], [6]
Mutation info Missense: L172P [8], [6]
Mutation info Missense: S67P [8], [6]
Mutation info Missense: V7G [8], [6]
Mutation info Missense: Y34S [8], [6]
Mutation info Nonsense: Y41 STOP [16], [8]
Mutation Frequency 1 out of 67 isolates
Mutation info Nonsense: Y99 STOP [11], [8]
Mutation info Missense: F94P [16], [6]
Mutation Frequency 1 out of 67 isolates
Mutation info Missense: H137R [16], [6]
Mutation Frequency 2 out of 67 isolates
Mutation info Missense: H57D [16], [6]
Mutation Frequency 2 out of 67 isolates
Mutation info Missense: L19P [16], [6]
Mutation Frequency 1 out of 67 isolates
Mutation info Missense: P54L [5], [6]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: P54T [16], [6]
Mutation Frequency 1 out of 67 isolates
Mutation info Missense: R121P [16], [6]
Mutation Frequency 1 out of 67 isolates
Mutation info Missense: T47A [16], [6]
Mutation Frequency 10 out of 67 isolates
Mutation info Missense: T76P [16], [6]
Mutation Frequency 1 out of 67 isolates
Mutation info Missense: V139A [16], [6]
Mutation Frequency 1 out of 67 isolates
Mutation info Missense: W119R [16], [6]
Mutation Frequency 1 out of 67 isolates
Mutation info Missense: W68L [16], [6]
Mutation Frequency 1 out of 67 isolates
Mutation info Missense: F80V [12]
Mutation info Missense: A3P [1]
Mutation info Missense: F13S [1]
Mutation info Missense: L182S [1]
Mutation info Missense: P69L [1]
Mutation info Frameshift: Plus 145 [1]
Mutation info Frameshift: Plus 64 [1]
Mutation info Frameshift: Plus 72 [1]
Mutation info Missense: T61P [1]
Mutation info Missense: T87M [1]
Mutation info Missense: Y103C [1]
Mutation info Missense: D49G [14]
Mutation info Frameshift: Plus 126 [14]
Mutation info Frameshift: Plus 28 [14]
Mutation info Nonsense: Q10 STOP [14]
Mutation info Missense: L120P [20]
Mutation info Missense: M1T [20]
Mutation info Frameshift: Plus 136 [15]
Mutation info Frameshift: Plus 171 [15]
Mutation info Frameshift: Plus 65 [15]
Mutation info Frameshift: Plus 74 [15]
Mutation info Missense: T142P [10]
Mutation info Missense: V155A [10]
Mutation info Missense: V7I [10]
Mutation info Frameshift: Plus 143 [13]
Mutation info Frameshift: Plus 17 [13]
Mutation info Missense: R140S [13]
Mutation info Nonsense: W68 STOP [13]
Mutation info Frameshift: Plus 167 [9]
Mutation info Frameshift: Plus 20 [9]
Mutation info Nonsense: S88 STOP [9]
Mutation info Missense: H57P [17]
Mutation info Missense: H82D [17]
Mutation info Frameshift: Plus 80 [17]
Mutation info Missense: S59P [17]
Mutation info Insertion: E/V/D129 [11]
Mutation info Missense: G97D [11]
Mutation info Missense: H71R [11]
Mutation info Missense: I133N [11]
Mutation info Missense: L4S [11]
Mutation info Missense: P62R [11]
Mutation info Frameshift: Plus 35 [11]
Mutation info Missense: T153N [11]
Mutation info Missense: V139G [11]
Mutation info Frameshift: Plus 29 [4]
Mutation info Missense: A25E [2]
Mutation info Missense: A28D [2]
Mutation info Missense: D8G [2]
Mutation info Missense: M1I [2]
Mutation info Frameshift: Plus 129 [2]
Mutation info Frameshift: Plus 131 [2]
Mutation info Frameshift: Plus 135 [2]
Mutation info Frameshift: Plus 138 [2]
Mutation info Frameshift: Plus 151 [2]
Mutation info Frameshift: Plus 155 [2]
Mutation info Frameshift: Plus 160 [2]
Mutation info Frameshift: Plus 177 [2]
Mutation info Frameshift: Plus 50 [2]
Mutation info Frameshift: Plus 53 [2]
Mutation info Nonsense: Q141 STOP [2]
Mutation info Missense: V9A [2]
Mutation info Nonsense: W119 STOP [2]
Mutation info Missense: Y64D [2]
Mutation info Missense: A171E [21]
Mutation info Missense: H51N [21]
Mutation info Missense: H82L [21]
Mutation info Missense: V128G [21]
Mutation info Missense: A46P [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: C14H [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: C72Y [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: D136G [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: D49H [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: E181D [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Nonsense: E37 STOP [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: G107K [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: H57Y [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: H71D [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: H71Y [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: L116V [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: L159P [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: L35R [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Frameshift: Plus 58 [5]
Mutation Frequency 63 out of 68 patients in all pncA mutations
Mutation info Missense: S179R [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: S185T [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: V9L [5]
Mutation Frequency 63 out of 68 isolates in all pncA mutations
Mutation info Missense: A79G [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: G162D [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: G17V [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: H57L [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: L19R [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: M75T [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: P62L [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Frameshift: Plus 16 [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Frameshift: Plus 22 [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: S185I [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: V21G [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: V9S [22]
Mutation Frequency 25% of the patients in all pncA mutations
Mutation info Missense: D53N [19]
Mutation info Frameshift: Plus 73 [19]
Mutation info Frameshift: Plus 147 [18]
Mutation Frequency 3 out of 48 patients
Mutation info Missense: V125G [18]
Mutation Frequency 19 out of 48 isolates
Mutation info Nonsense: Y95 STOP [18]
Mutation info Missense: L35P [23]
Mutation info Missense: W119C [23]
Mutation info Missense: D63H [7]
Mutation info Missense: D8E [3]
Mutation info Missense: K96T [3]
Mutation info Frameshift: Plus 104 [3]
Mutation info Frameshift: Plus 10 [3]
Mutation info Frameshift: Plus 139 [3]
Mutation info Frameshift: Plus 148 [3]
Mutation info Frameshift: Plus 158 [3]
Mutation info Frameshift: Plus 173 [3]
Mutation info Frameshift: Plus 33 [3]
Mutation info Frameshift: Plus 34 [3]
Mutation info Insertion: R/S/M129 [16]
Mutation info Missense: A146V [8]
Mutation info Missense: D63G [8]
Mutation info Missense: G132D [8]
Mutation info Missense: H43P [8]
Mutation info Missense: H51P [8]
Mutation info Missense: H51R [8]
Mutation info Frameshift: Plus 46 [8]
Mutation info Missense: S104R [8]
Mutation info Missense: T114P [8]
Mutation info Missense: T142A [8]
Mutation info Missense: V130G [8]
Mutation info Missense: D12E [6]
Mutation info Missense: L27P [6]
Mutation info Missense: M1S [6]
Mutation info Missense: S104C [6]
References
REF 1 Characterization of new mutations in pyrazinamide-resistant strains of Mycobacterium tuberculosis and identification of conserved regions important for the catalytic activity of the pyrazinamidase PncA. Antimicrob Agents Chemother. 1999 Jul;43(7):1761-3.
REF 2 Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Korea. J Korean Med Sci. 2001 Oct;16(5):537-43.
REF 3 Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1997 Mar;41(3):540-3.
REF 4 Pyrazinamide-monoresistant Mycobacterium tuberculosis in the United States. J Clin Microbiol. 2001 Feb;39(2):647-50.
REF 5 Frequency and implications of pyrazinamide resistance in managing previously treated tuberculosis patients. Int J Tuberc Lung Dis. 2006 Jul;10(7):802-7.
REF 6 The comprehensive antibiotic resistance database. Antimicrob Agents Chemother. 2013 Jul;57(7):3348-57.
REF 7 Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus. Nat Med. 1996 Jun;2(6):662-7.
REF 8 Mutation in pncA is a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis. Tuber Lung Dis. 1997;78(2):117-22.
REF 9 Molecular characterization of pncA gene mutations in Mycobacterium tuberculosis clinical isolates from China. Epidemiol Infect. 2000 Apr;124(2):227-32.
REF 10 Genotypic characterization of drug-resistant Mycobacterium tuberculosis isolates from Peru. Tuber Lung Dis. 1998;79(2):111-8.
REF 11 Characterization of spontaneous, In vitro-selected, rifampin-resistant mutants of Mycobacterium tuberculosis strain H37Rv. Antimicrob Agents Chemother. 2000 Dec;44(12):3298-301.
REF 12 Novel pncA Mutations in Pyrazinamide-Resistant Isolates of Mycobacterium tuberculosis. Mol Diagn. 1998 Dec;3(4):229-231.
REF 13 pncA mutations as a major mechanism of pyrazinamide resistance in Mycobacterium tuberculosis: spread of a monoresistant strain in Quebec, Canada. Antimicrob Agents Chemother. 2000 Mar;44(3):528-32.
REF 14 pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis isolates from northwestern Russia. Antimicrob Agents Chemother. 1999 Jul;43(7):1764-6.
REF 15 Relationship between pyrazinamide resistance, loss of pyrazinamidase activity, and mutations in the pncA locus in multidrug-resistant clinical isolates of Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1999 Sep;43(9):2317-9.
REF 16 Mutations associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complex organisms. Antimicrob Agents Chemother. 1997 Mar;41(3):636-40.
REF 17 Simultaneous identification and typing of multi-drug-resistant Mycobacterium tuberculosis isolates by analysis of pncA and rpoB. J Med Microbiol. 2000 Jul;49(7):651-6.
REF 18 Multidrug-resistant tuberculosis in Lisbon, Portugal: a molecular epidemiological perspective. Microb Drug Resist. 2008 Jun;14(2):133-43.
REF 19 Development and evaluation of a line probe assay for rapid identification of pncA mutations in pyrazinamide-resistant mycobacterium tuberculosis st... J Clin Microbiol. 2007 Sep;45(9):2802-7.
REF 20 Discrimination of multidrug-resistant Mycobacterium tuberculosis IS6110 fingerprint subclusters by rpoB gene mutation analysis. J Clin Microbiol. 1999 Sep;37(9):3022-4.
REF 21 Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis in Brazil. Antimicrob Agents Chemother. 2005 Jan;49(1):444-6.
REF 22 Genetic and phenotypic characterization of drug-resistant Mycobacterium tuberculosis isolates in Hong Kong. J Antimicrob Chemother. 2007 May;59(5):866-73.
REF 23 In-depth molecular characterization of Mycobacterium tuberculosis from New Delhi--predominance of drug resistant isolates of the 'modern' (TbD1) type. PLoS One. 2009;4(2):e4540.

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