It is unknown whether MIRU-VNTR (Mycobacterial Interspersed Repetitive Unit-Variable Number of Tandem Repeat) is associated with drug resistance of Mycobacterium tuberculosis. The purpose of this study was to explore the ability of 24 MIRU loci to predict the drug resistance of Isoniazid (INH), Rifampicin (RFP), Streptomycin (SM), Ethambutol (EMB) and Pyrazinamide (PZA). We collected the drug r...

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. ...

Mycobacterium tuberculosis 18b, a streptomycin (STR)-dependent mutant that enters a viable but nonreplicating state in the absence of STR, has been developed as a simple model for drug testing against dormant bacilli. Here, we further evaluated the STR-starved 18b (SS18b) model both in vitro and in vivo by comparing the behavior of 22 approved and experimental tuberculosis drugs. Using the resa...

PURPOSE The purpose of this study was to determine the activity of pyrazoloacridine (PZA) in neuroblastomas that have acquired high-level resistance to multiple drugs (not associated with multidrug resistance-associated protein or P-glycoprotein) during therapy, including those with loss of p53 function. EXPERIMENTAL DESIGN We determined the activity of PZA in 12 drug-sensitive and 10 multidr...

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 ...

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...