An optimal assay for high-throughput screening for new antituberculosis agents would combine the microplate format and low cost of firefly luciferase reporter assays and redox dyes with the ease of kinetic monitoring inherent in the BACTEC system. The green fluorescent protein (GFP) of the jellyfish Aequorea victoria is a useful reporter molecule which requires neither substrates nor cofactors ...

BACKGROUND Since the sterilising activity of new antituberculosis drugs is difficult to assess by conventional phase III studies, surrogate methods related to eventual relapse rates are required. METHODS A suitable method is suggested by a retrospective analysis of viable counts of Mycobacterium tuberculosis in 12-hr sputum collections from 122 newly diagnosed patients with pulmonary tubercul...

BACKGROUND Treatment of multidrug-resistant or extensively drug-resistant tuberculosis (DR-tuberculosis) is challenging because commonly used second-line drugs are poorly efficacious and highly toxic. Although World Health Organization group 5 drugs are not recommended for routine use because of unclear activity, some may have untapped potential as more efficacious or better tolerated alternati...

The in vitro activity of 16 antimicrobial agents against 46 drug-resistant strains of Mycobacterium tuberculosis recently isolated from Italian patients was determined. As for first-line antituberculosis drugs, while isoniazid was ineffective against all the strains tested, resistance to streptomycin, rifampicin, pyrazinamide, and ethambutol was 80.4%, 71.7%, 39.1%, and 8.7%, respectively. Amon...

Ethionamide (ETA) is an important component of second-line therapy for the treatment of multidrug-resistant tuberculosis. Synthesis of radiolabeled ETA and an examination of drug metabolites formed by whole cells of Mycobacterium tuberculosis (MTb) have allowed us to demonstrate that ETA is activated by S-oxidation before interacting with its cellular target. ETA is metabolized by MTb to a 4-py...

INTRODUCTION In people infected with both HIV and Mycobacterium tuberculosis, the annual risk of developing active tuberculosis is 5% to 10% - more than 10 times the rate for HIV-negative people with M tuberculosis infection. Untreated, mortality from tuberculosis in people with HIV is likely to be high, and over 5% of people relapse after successful treatment. METHODS AND OUTCOMES We conduct...

The metabolism of the anti-tubercular drug, thiacetazone (TAZ) by human FMOs in vitro and the disposition of TAZ in vivo in mice were studied. Reverse phase chromatography confirmed TAZ to be a substrate for human FMO1, FMO2.1 and FMO3 with the formation of TAZ-sulphinic acid and TAZ-carbodiimide via a TAZsulphenic acid intermediate. The products are the same as those formed by the Mycobacteriu...

OBJECTIVES In vitro studies have shown good activity of linezolid against Mycobacterium tuberculosis, including multidrug-resistant strains. However, clinical experience with linezolid in tuberculosis is scarce. METHODS We report our clinical experience with five consecutive patients with multidrug-resistant tuberculosis infection treated with combination regimens that included linezolid. R...

Tuberculosis (TB) is most probably the disease that has caused more damage to the human species throughout its history in terms of number of patients and, above all, death toll. There have been thousands of years spent fighting against Mycobacterium tuberculosis in which the human species could only rely on the efficiency of the immune system [1]. We must recall its importance as, in the pre-an...