BACKGROUND Pyrazinamide is a paradoxical frontline tuberculosis drug characterized by high in vivo sterilizing activity but poor in vitro activity. This separation in pyrazinamide activity reflects differences between the in vivo tissue environment and in vitro culture conditions. The well-known acid pH requirement for pyrazinamide activity was discovered previously based on such reasoning but ...

Despite the important role of pyrazinamide in tuberculosis treatment, little is known about the mechanism of pyrazinamide-induced hepatotoxicity. We inhibited xanthine oxidase in HepG2 cells by using a nontoxic concentration of allopurinol, a well-known xanthine-oxidase inhibitor. This increased in vitro pyrazinamide toxicity in HepG2 cells, which suggests that the hydroxy metabolites of pyrazi...

BACKGROUND Pyrazinamide is a paradoxical frontline tuberculosis drug characterized by high sterilizing in vivo activity but poor in vitro activity. Pyrazinamide is thought to act by the entrapment of pyrazinoic acid in the bacterial cell, leading to acidification and membrane damage. Consequently, the effects of weak acids and molecules affecting membranes added to pyrazinamide were studied. ...

The role of pyrazinamide in the current treatment of multidrug-resistant (MDR) tuberculosis (TB) is uncertain. From a territory-wide registry of MDR-TB cases diagnosed between 1995 and 2009, we assembled a cohort of 194 patients with MDR pulmonary TB given fluoroquinolone-containing regimens. Stratified by pyrazinamide use and susceptibility, there were 83 users with pyrazinamide-susceptible MD...

Pyrazinamide is an important sterilizing drug that shortens tuberculosis (TB) therapy. However, the mechanism of action of pyrazinamide is poorly understood because of its unusual properties. Here we show that pyrazinoic acid, the active moiety of pyrazinamide, disrupted membrane energetics and inhibited membrane transport function in Mycobacterium tuberculosis. The preferential activity of pyr...

Pyrazinamidase activity has been associated with pyrazinamide-susceptible Mycobacterium tuberculosis strains. The detection of pyrazinamidase activity by the Wayne method was found to be of limited value when compared with the results of standard pyrazinamide susceptibility tests, especially when a high level of pyrazinamide resistance was found. When resistance to pyrazinamide reached a level ...

Background: Pyrazinamide is one of the most important first-line medications for treatment tuberculosis and an alternative intake MDR-TB XDR-TB patients. Objectives: The purpose this study was to evaluate resistance pyrazinamide in isolates resistant Mycobacterium drug patients city Isfahan. Methods: In study, susceptibility test performed with using proportion method PZA assay on 47 tuberculos...

The mechanism of action of pyrazinamide, a key sterilizing drug in the treatment of tuberculosis, remains elusive; pyrazinamide is a pro-drug that requires activation by a bacterial-encoded enzyme, and its activity is most apparent on non-replicating Mycobacterium tuberculosis. Recently, it has been suggested that pyrazinamide might exert also some host-directed effect in addition to its antimi...

20 Patients of tuberculous pleural effusion were administered a combination of pyrazinamide (30 mg/kg) + isoniazid (300 mg) orally for 7 consecutive days and pyrazinamide was estimated by spectrophotometric method in serum and pleural fluid. Prednisolone was added to the above regimen for next 7 consecutive days and pyrazinamide was again estimated. The level of pyrazinamide in pleural fluid wa...