title: Challenges, successes and hopes in the development of novel TB therapeutics.
abstract: Despite efficacious drugs for treatment, TB continues to affect enormous numbers of patients throughout the world. Failure to control TB may be related to the biological characteristics of Mycobacterium tuberculosis, the nature of susceptible hosts often impoverished and poorly supported by healthcare infrastructure and the complex treatment regimens that must be used. Challenges to anti-TB drug development include the organism's slow replication, the ability of M. tuberculosis to survive in a dormant state and to persist despite therapy, its impregnable cell wall and its capacity to develop resistance to drugs. The need for extended therapy using combinations of drugs remains a practical obstacle to effective control in poor, malnourished and diseased communities most susceptible to TB. High-throughput screening of candidate agents and investigation of drugs already in use for other infections are yielding promising new candidates for TB treatment. New families of drugs entering clinical trials include 5-nitroimidazoles, diarylquinolines and ethylene diamines. Increasing funding initiatives, advances in the biology of TB and strategies for drug discovery have rejuvenated the pipeline of new drugs for TB, promising an expanding armamentarium of effective drugs with improved tolerability and potential to treat drug-resistant cases.
authors.affiliation: Office of Critical Path Programs, US FDA, Room 14B45, 5600 Fishers Lane, Rockville, MD 20857, USA. leonard.sacks@fda.hhs.gov
authors.forename: Leonard V
authors.initials: LV
authors.lastname: Sacks
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Behrman
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D057166:High-Throughput Screening Assays; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000235:genetics / Q000254:growth & development; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents