Disease relevance of pyrazinamide

• HIV-seropositive and HIV-seronegative outpatients with pulmonary tuberculosis were treated with rifampin, isoniazid, pyrazinamide, and ethambutol daily for two months, followed by rifampin plus isoniazid twice weekly for four months [1].
• Naturally pyrazinamide (PZA)-resistant Mycobacterium bovis and acquired PZA-resistant M. tuberculosis strains lose pyrazinamidase (PZase) [2].
• In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01) [3].
• Drug-resistant tuberculosis: inconsistent results of pyrazinamide susceptibility testing [4].
• Acute hypertension as an adverse effect of pyrazinamide [5].

Psychiatry related information on pyrazinamide

• Then patients stopped pyrazinamide and ethambutol and started once-daily antiretroviral therapy (ART) with didanosine, lamivudine, ritonavir (200 mg) and saquinavir (1600 mg) (second PK study, n = 18) [6].

High impact information on pyrazinamide

• The relative risk of tuberculosis with isoniazid alone, as compared with placebo, was 0.33 (95 percent confidence interval, 0.14 to 0.77); with isoniazid and rifampin, 0.40 (0.18 to 0.86); and with isoniazid, rifampin, and pyrazinamide, 0.51 (0.24 to 1.08) [7].
• Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus [2].
• In Transkei, 143 patients with active tuberculous constrictive pericarditis without significant pericardial effusion all received the same daily 6-month antituberculosis regimen of streptomycin, isoniazid, rifampicin, and pyrazinamide for 14 weeks followed by isoniazid and rifampicin [8].
• RESULTS: Reduced total drug exposure to rifampin and pyrazinamide was associated with D-xylose malabsorption in persons with HIV infection or AIDS [9].
• The aim of this study was to assess the prognostic influence of pyrazinamide on the outcome of fulminant or subfulminant liver failure caused by antituberculous therapy [10].

Chemical compound and disease context of pyrazinamide

• Following 9 months of treatment with isoniazid, ethambutol, rifampin, and pyrazinamide, most lesions resolved; however, one cortical tuberculoma enlarged significantly [11].
• Sixteen patients with oral isoniazid, pyrazinamide, rifampin, and intramuscular streptomycin for tuberculous meningitis were studied [12].
• Bacterial pyrazinamidase (PZAase)/nicotinamidase converts pyrazinamide (PZA) to ammonia and pyrazinoic acid, which is active against Mycobacterium tuberculosis [13].
• Structural analogues of amiloride without significant activity at the Na+/H+ antiport (pyrazine, pyrazinamide, and chloropyrazine) failed to inhibit contact hypersensitivity [14].
• Synergistic activities of clarithromycin and pyrazinamide against Mycobacterium tuberculosis in human macrophages [15].

Biological context of pyrazinamide

• Reduced pyrazinamidase activity and the natural resistance of Mycobacterium kansasii to the antituberculosis drug pyrazinamide [16].
• We examined the correlation of mutations in the pyrazinamidase (PZase) gene (pncA) with the pyrazinamide (PZA) resistance phenotype with 60 Mycobacterium tuberculosis isolates [17].
• Pyrazinamide, a drug structurally related to INH, also mimicked its effect on electron transport particles [18].
• In macrophage cultures, serial concentrations of isoniazid, rifampin, pyrazinamide, or streptomycin were added after a 2.5-h phagocytosis period [19].
• In an attempt to investigate the molecular basis of pyrazinamide hydrolysis by the PncA protein from Mycobacterium tuberculosis, we determined the pyrazinamidase activity of nine PncA mutants bearing a single amino acid substitution [20].

Anatomical context of pyrazinamide

• CONCLUSIONS: The addition of moxifloxacin to isoniazid, rifampin, and pyrazinamide did not affect 2-mo sputum culture status but did show increased activity at earlier time points [21].
• The concentrations of isoniazid, pyrazinamide, rifampin, and streptomycin in cerebrospinal fluid (CSF) obtained 3 hours after administration were 2.40, 34.78, 0.29, and 3.78 micrograms/ml, respectively [12].
• Colony-forming units of Mycobacterium tuberculosis in sputum were counted at 2-day intervals in 100 patients treated with 22 regimens of isoniazid, rifampin, pyrazinamide, ethambutol, or streptomycin, given alone or in combinations [22].
• Pyrazinamide was only bacteriostatic in macrophages but weakly bactericidal during the first day of exposure in vitro [19].
• The combination of RFP, isoniazid (INH), and pyrazinamide (PZA) administered daily resulted in an apparent clearance of M. tuberculosis organisms in the lungs and spleens of infected mice after 10 weeks of treatment [23].

Associations of pyrazinamide with other chemical compounds

• Subjects with positive tuberculin skin tests (induration, > or =5 mm) with purified protein derivative (PPD) were randomly assigned to one of four regimens: placebo (464 subjects), isoniazid daily for six months (536), isoniazid and rifampin daily for three months (556), or isoniazid, rifampin, and pyrazinamide daily for three months (462) [7].
• The uric acid clearance decreased to low or normal values after pyrazinamide administration [24].
• In contrast to healthy subjects, the CUA/Ccr of patients with homozygous and compound heterozygous SLC22A12 mutations was unaffected by pyrazinamide, benzbromarone, and probenecid [25].
• The organisms showed in vitro resistance in eight patients to rifampicin, in 19 patients to isoniazid, and in all patients to pyrazinamide and p-aminosalicylic acid [26].
• Using this purified enzyme, in vitro conversion of allopurinol, pyrazinamide and pyrazinoic acid was investigated [27].

Gene context of pyrazinamide

• Characterization of pncA mutations in pyrazinamide-resistant Mycobacterium tuberculosis in Brazil [28].
• Escherichia coli isolates expressing individually five of the eight katG mutations showed loss of catalase and INH oxidation activities, and isolates carrying any of the five pncA mutations showed no pyrazinamidase activity, indicating that these mutations are associated with INH and PZA resistance, respectively [29].
• Allopurinol or pyrazinamide was administered to rats treated with BOF-4272 (a potent xanthine oxidase inhibitor) to investigate to what degree xanthine dehydrogenase participates in the oxidation of these agents [30].
• Besides biochemical (sensitivity to pyrazinamide) and epidemiological features, strains of this unusual member of the M. tuberculosis complex show a special combination of pncA, oxyR, katG and gyrA gene polymorphisms [31].
• In Mycobacterium tuberculosis there is a strong correlation between in-vitro resistance to rifampicin (RIF) and pyrazinamide (PZA) and mutations in rpoB and pncA, respectively [32].

Analytical, diagnostic and therapeutic context of pyrazinamide

• In these patients, pyrazinamide administration and an interval of more than 15 days between the onset of antituberculous treatment and jaundice, combined with grade III encephalopathy and factor V below 20%, predicted death without liver transplantation [10].
• Levels of resistance in new and retreatment TB cases to 1 or more of the 3 current first-line drugs used in Mexico (isoniazid, rifampin, and pyrazinamide) were 12.9% and 50.5%, respectively; the corresponding levels of multi-drug-resistant TB were 2.4% and 22.4% [33].
• The CSF concentrations of isoniazid and pyrazinamide were well above the minimum inhibitory concentration for Mycobacterium tuberculosis [12].
• Pyrazinamide was measured by high-performance liquid chromatography [34].
• Nevertheless, all patients showed an early response to standard combination chemotherapy with rifampicin, isoniazid, and ethambutol, with or without pyrazinamide [26].

References