Pyrazinamide (PZA) is an important front line anti-tuberculosis drug because of its sterilizing activity against semi-dormant tubercle bacilli. In spite of its remarkable role in shortening the treatment duration from 9 months to 6 months when used in combination with Rifampicin and Isoniazid, PZA remains a difficult paradox because of its incompletely understood mode of action and mechanism of...

Unlike most other bacteria, mycobacteria make fatty acids with the multidomain enzyme eukaryote-like fatty acid synthase I (FASI). Previous studies have demonstrated that the tuberculosis drug pyrazinamide and 5-chloro-pyrazinamide target FASI activity. Biochemical studies have revealed that in addition to C(16:0), Mycobacterium tuberculosis FASI synthesizes C(26:0) fatty acid, while the Mycoba...

RATIONALE The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model. OBJECTIVE AND METHODS Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment fo...

Tuberculosis (TB), caused by strains of Mycobacterium tuberculosis complex (M. tuberculosis), is a pulmonary infection that is spread by airborne droplet transmission. The development and spread of drug-resistant strains of M. tuberculosisgreatly jeopardize TB control efforts. We report the case of a previously healthy 43-year-old male, visiting from China, who presented to the emergency depart...

Motivation Correct and rapid determination of Mycobacterium tuberculosis (MTB) resistance against available tuberculosis (TB) drugs is essential for the control and management of TB. Conventional molecular diagnostic test assumes that the presence of any well-studied single nucleotide polymorphisms is sufficient to cause resistance, which yields low sensitivity for resistance classification. ...

New regimens based on two or more novel agents are sought in order to shorten or simplify the treatment of both drug-susceptible and drug-resistant forms of tuberculosis. PA-824 is a nitroimidazo-oxazine now in phase II trials and has shown significant early bactericidal activity alone and in combination with the newly approved agent bedaquiline or with pyrazinamide with or without moxifloxacin...

The activities of some commonly used antituberculosis drugs were investigated within unstimulated peritoneal macrophages and in 7H-9 medium without Tween 80 using Mycobacterium microti OV254 as the target organism. In macrophage cultures, serial concentrations of isoniazid, rifampin, pyrazinamide, or streptomycin were added after a 2.5-h phagocytosis period. Viable counts were carried out at da...

BACKGROUND Tuberculosis is one of the major public health problems worldwide. Modern antituberculous treatment can cure most patients; cure rates > 95% are achieved with standard short-course chemotherapy regimens containing isoniazid, rifampicin, pyrazinamide, and ethambutol among patients with drug-susceptible strains of tuberculosis; however, a small proportion do not respond to treatment or...