New Regimens for Reducing the Duration of Treatment of Drug-Susceptible Pulmonary Tuberculosis

Tuberculosis (TB) remains an important health problem worldwide. The structure necessary for delivering TB treatment and implementing the directly observed treatment accounts for more than two-thirds of its final cost. Furthermore, although with efficacy greater than 90%, the effectiveness of present treatment regimens ranges within 55-85%, depending on the setting, mainly because of poor adherence. Duration of treatment with the current first-line anti-TB drugs is a minimum of 6 months. Reducing the duration of treatment from 6 to 2 months or less could result in significant increase of adherence to treatment and cost reduction. The aim of this review is to highlight potential new agents or new drug combinations that could reduce the time of treatment of drug-susceptible TB, currently under study or recently evaluated through clinical trials. We conducted a literature search in the English language for clinical studies as well as an electronic computer-assisted and manual search. The literature search was conducted in November 2010, using MEDLINE (2000-2010), EMBASE (2000-2010), and the National Institutes of Health (NIH) Clinical Trials Register database (2000-2010). Most of the new agents identified as anti-TB drug candidates are still in the preclinical phases. Nitroimidazole-PA-824 and fluoroquinolones are evaluated, whereas two first-line drugs (i.e., rifampicin and rifapentine) are reevaluated to optimize their efficacy in new ultra-short anti-TB regimens through phase II/III clinical studies. A summary of the studies is presented, with their potential to change recommendations for TB treatment in the near future. Drug Dev Res 72: 501-508, 2011. (C) 2011 Wiley-Liss, Inc.