Tuberculosis drug development: progress, challenges, and the road ahead
- PMID: 20382086
- DOI: 10.1016/j.tube.2010.03.003
Tuberculosis drug development: progress, challenges, and the road ahead
Abstract
Tuberculosis (TB) drug development has made substantial progress in the past decade. There are currently at least ten drugs being evaluated in clinical trials. Some belong to chemical classes already employed in first- or second-line treatment regimens and are being explored for more optimized use at higher doses or in new drug combinations (rifamycins, fluoroquinolones and oxazolidinones), while others represent potential novel members of the TB drug arsenal, killing Mycobacterium tuberculosis through previously untried mechanisms of action (nitroimidazoles, diarylquinolines, ethylene diamines and pyrroles). The typical challenges of drug development are augmented in TB by the complexity of the disease, the requirement for multi-drug regimens, the relative lack of TB drug development for the past several decades, and inadequate resources being brought to bear despite the urgency of the global medical need. Yet in the face of these challenges, for the first time in history, there is a robust enough pipeline of drugs in development to potentially enable identification of a novel, three-drug regimen capable of curing patients in three months or less, whether they are infected with a strain of M. tuberculosis sensitive or resistant to the current first and second-line drugs. Realizing this potential will require innovation, persistence, cooperation and resources. A fine balance will need to be achieved between protecting novel drugs so that resistance to them doesn't develop and ensuring the regimens are low in cost, readily available, and adopted by healthcare systems and providers.
Copyright 2010 Elsevier Ltd. All rights reserved.
Similar articles
-
[Development of antituberculous drugs: current status and future prospects].Kekkaku. 2006 Dec;81(12):753-74. Kekkaku. 2006. PMID: 17240921 Review. Japanese.
-
New drugs and new regimens for the treatment of tuberculosis: review of the drug development pipeline and implications for national programmes.Curr Opin Pulm Med. 2010 May;16(3):186-93. doi: 10.1097/MCP.0b013e328337580c. Curr Opin Pulm Med. 2010. PMID: 20216421 Review.
-
[Frontier of mycobacterium research--host vs. mycobacterium].Kekkaku. 2005 Sep;80(9):613-29. Kekkaku. 2005. PMID: 16245793 Japanese.
-
Challenges, successes and hopes in the development of novel TB therapeutics.Future Med Chem. 2009 Jul;1(4):749-56. doi: 10.4155/fmc.09.53. Future Med Chem. 2009. PMID: 21426037 Review.
-
Mycobacterium tuberculosis: drug resistance and future perspectives.Future Microbiol. 2009 Jun;4(5):597-614. doi: 10.2217/fmb.09.20. Future Microbiol. 2009. PMID: 19492969 Review.
Cited by
-
A physiologically based pharmacokinetic model of rifampin in mice.Antimicrob Agents Chemother. 2013 Apr;57(4):1763-71. doi: 10.1128/AAC.01567-12. Epub 2013 Jan 28. Antimicrob Agents Chemother. 2013. PMID: 23357766 Free PMC article.
-
New classes of alanine racemase inhibitors identified by high-throughput screening show antimicrobial activity against Mycobacterium tuberculosis.PLoS One. 2011;6(5):e20374. doi: 10.1371/journal.pone.0020374. Epub 2011 May 26. PLoS One. 2011. PMID: 21637807 Free PMC article.
-
Population-level impact of shorter-course regimens for tuberculosis: a model-based analysis.PLoS One. 2014 May 9;9(5):e96389. doi: 10.1371/journal.pone.0096389. eCollection 2014. PLoS One. 2014. PMID: 24816692 Free PMC article.
-
New drugs and regimens for treatment of TB.Expert Rev Anti Infect Ther. 2010 Jul;8(7):801-13. doi: 10.1586/eri.10.60. Expert Rev Anti Infect Ther. 2010. PMID: 20586565 Free PMC article. Review.
-
Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis.N Engl J Med. 2014 Oct 23;371(17):1577-87. doi: 10.1056/NEJMoa1407426. Epub 2014 Sep 7. N Engl J Med. 2014. PMID: 25196020 Free PMC article. Clinical Trial.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous