Managing TB in the 21st century: existing and novel drug therapies

With an estimated one-third of the world's population infected with Mycobacterium tuberculosis (MTB) and approximately 1.6 million deaths in 2006 attributed to tuberculosis (TB) world-wide, TB remains a major public health concern today. Considerable advances have been made in the effective treatment of TB, in particular with the adoption of directly observed therapy short course (DOTS), in national TB control programs, but in spite of this the currently available regimens are suboptimal. The long courses of therapy required, together with significant medication side-effects and resulting difficulties with adherence to therapy all contribute to increasing problems with emerging drug resistance. There is thus an urgent need for new antituberculous drug development, especially to enable effective shorter course therapy for drug-susceptible and resistant TB, to find effective drugs for treatment of drug-resistant TB, to shorten therapy for latent TB infection and to reduce drug interactions in combination with antiretroviral therapy, a major issue in the treatment of HIV co-infected patients. This review will attempt to summarize the current recommendations for treatment of TB and then describe the most promising new antimicrobials with activity against MTB, focusing on the ones currently undergoing clinical trials.