14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial.

Background: New drugs, but also shorter, better-tolerated regimens are needed to tackle the high global burden of tuberculosis complicated by drug resistance and retroviral disease. We investigated new multiple-agent combinations over the first 14 days of treatment to assess their suitability for future development.

Methods: In this prospective, randomised, early bactericidal activity (EBA) study, treatment-naive, drug-susceptible patients with uncomplicated pulmonary tuberculosis were admitted to hospitals in Cape Town, South Africa, between Oct 7, 2010, and Aug 19, 2011.

Phase II dose-ranging trial of the early bactericidal activity of PA-824.

PA-824 is a novel nitroimidazo-oxazine under evaluation as an antituberculosis agent. A dose-ranging randomized study was conducted to evaluate the safety, tolerability, pharmacokinetics, and early bactericidal activity of PA-824 in drug-sensitive, sputum smear-positive adult pulmonary-tuberculosis patients to find the lowest dose giving optimal bactericidal activity (EBA). Fifteen patients per cohort received oral PA-824 in doses of 50 mg, 100 mg, 150 mg, or 200 mg per kg body weight per day for 14 days.

Current development and future prospects in chemotherapy of tuberculosis.

Although treatment of drug-susceptible tuberculosis (TB) under ideal conditions may be successful in >or=95% of cases, cure rates in the field are often significantly lower due to the logistical challenges of administering and properly supervising the intake of combination chemotherapy for 6-9 months. Success rates are far worse for multidrug-resistant and extensively drug-resistant TB cases. There is general agreement that new anti-TB drugs are needed to shorten or otherwise simplify treatment for drug-susceptible and multidrug-resistant/extensively drug-resistant-TB, including TB associated with HIV infection.

Early bactericidal activity and pharmacokinetics of PA-824 in smear-positive tuberculosis patients.

PA-824 is a novel nitroimidazo-oxazine being evaluated for its potential to improve tuberculosis (TB) therapy. This randomized study evaluated safety, tolerability, pharmacokinetics, and extended early bactericidal activity of PA-824 in drug-sensitive, sputum smear-positive, adult pulmonary tuberculosis patients. Fifteen patients per cohort received 1 of 4 doses of oral PA-824: 200, 600, 1,000, or 1,200 mg per day for 14 days.

Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects.

PA-824 is a novel antibacterial agent that has shown in vitro activity against both drug-sensitive and drug-resistant Mycobacterium tuberculosis. The compound's MIC is between 0.015 and 0.

New tuberculosis therapeutics: a growing pipeline.

Novel chemotherapeutic drugs are needed to improve tuberculosis (TB) control, especially in the developing world. Given the magnitude of the problem and the resources available in countries that have the highest burden of disease, the present standards of care for the treatment of drug-susceptible TB, drug-resistant TB, TB/human immunodeficiency virus (HIV) coinfection, and latent TB infection are all unsatisfactory. Because no truly novel compounds for the treatment of TB have been discovered in the past 40 years, the recent enhanced activity in the research and development of new TB drugs is extremely encouraging.