Exposure to lower-than-therapeutic levels of anti-tuberculosis drugs is likely to cause selection of resistant strains of Mycobacterium tuberculosis and treatment failure. The first-line anti-tuberculosis (TB) regimen consists of rifampicin, isoniazid, pyrazinamide, and ethambutol, and correct management reduces risk of TB relapse and development of drug resistance. In this study we aimed to in...

Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations in pncA offers the potential for rapid detection of pyrazinamide resistance (PZA(r)). However, the genetic variants are highly variable and scattered over the full length of pncA, complicating the develop...

Although clofazimine is used to treat multidrug-resistant tuberculosis (MDR-TB), there is scant information on its effectiveness and safety. The aim of this retrospective, observational study was to evaluate these factors as well as the tolerability of clofazimine in populations in Brazil, where it was administered at a daily dose of 100 mg·day-1 (body weight ≥45 kg) as part of a standardised M...

Recent pharmacokinetic studies that included children found that serum drug levels were low compared to those of adults for whom the same dosages were used. This study aimed to characterize the pharmacokinetics of pyrazinamide and ethambutol in Malawian children and to examine the impact of age, nutritional status, and human immunodeficiency virus (HIV) infection. We conducted a pharmacokinetic...

Combination therapy with anti-HIV drugs and opportunistic infection drugs is a common practice in treatment of AIDS patients. Although toxic effects of most individual therapies are known, the toxic potential of most combination therapies has not been established. To understand the toxic consequences of combination therapies, the commonly used anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) and ...

The reliability of the MB/BACT system for susceptibility testing of Mycobacterium tuberculosis to pyrazinamide, rifampin, isoniazid, streptomycin, and ethambutol was compared to the BACTEC 460TB system. The proportion method was used to resolve discrepant results by an independent arbiter. Two interpretative methods were used, with an undiluted control (direct control) and a diluted control (10...

treatment of tuberculosis (tb) and the discovery of effective new anti tubercular drugs is one of the most urgent priorities in health organizations all around the world. in the present study, fluorinated analogs of some of the most important anti-tb agents such as p-aminosalicylic acid (pas), thiacetazone and pyrazinamide were synthesized and tested against tb. the fluorinated analog of thiace...

OBJECTIVES to explore the effect of low incubation temperatures and the consequent slowing of bacterial metabolism on the bactericidal action of anti-tuberculosis drugs against Mycobacterium tuberculosis. METHODS counting of surviving bacteria during exposure of static cultures to 1 mg/L isoniazid, 2 mg/L rifampicin, 0.5 or 2 mg/L TMC207 and 40 or 160 mg/L pyrazinamide, usually for periods of...

OBJECTIVES Pharmacokinetic drug-drug interactions were investigated between the fluoroquinolone gatifloxacin and a fixed dose combination (FDC) of rifampicin, isoniazid and pyrazinamide. PATIENTS AND METHODS The single-dose pharmacokinetics of the four drugs was evaluated in an open-label three-way cross-over study amongst 22 healthy volunteers following administration of gatifloxacin, the FD...

In spite of the recent introduction of two new drugs (delamanid and bedaquiline) and a few repurposed compounds to treat multidrug-resistant and extensively drug-resistant tuberculosis (MDR- and XDR-TB), clinicians are facing increasing problems in designing effective regimens in severe cases. Recently a 9 to 12-month regimen (known as the 'Bangladesh regimen') proved to be effective in treatin...