Advancing the development of tuberculosis therapy

  title={Advancing the development of tuberculosis therapy},
  author={Alimuddin Zumla and Richard Hafner and Christian Lienhardt and Michael Hoelscher and Andrew J Nunn},
  journal={Nature Reviews Drug Discovery},
Although the development of novel drugs and combination regimens for tuberculosis has accelerated in recent years, the pipeline remains thin and major challenges remain to be addressed in efficiently evaluating newer drugs to improve treatment outcomes, shorten duration of therapy and tackle drug resistance. 
Using combination therapy to thwart drug resistance.
Modeling of interactions between drugs has provided intriguing insights into strategies for combination therapy deployment, but more rigorous clinical trials need to be performed to evaluate the laboratory and modeling results and advance treatment options.
Challenges and opportunities in tuberculosis drug discovery: an industry perspective "Frequently, the hit rate for target-based screens, which deal with a single-gene target, is significantly lower compared with random whole cell-based screens."
, a diarylquinolone antimycobacterial drug for treating multidrug-resistant TB. This approval has come with a heavy burden for post-market-ing studies and it remains to be seen whether the drug will
Is adjuvant therapy a potential road for fighting Mycobacterium tuberculosis resistance?
  • M. Martins
  • Biology, Medicine
    Expert review of anti-infective therapy
  • 2012
The unavoidable emergence of highly drug resistant (MDR, XDR and TDR) strains has lead to a real urgency in the search for new and more active compounds.
Antimicrobial peptides as novel anti-tuberculosis therapeutics.
Newer Anti-TB Drugs and Drug Delivery Systems
Evidence is summarized regarding the efficacy and potential of repurposed existing anti- TB drugs and emerging new anti-TB drug molecules in the treatment of active TB disease.
Epistasis between antibiotic resistance mutations drives the evolution of extensively drug-resistant tuberculosis
The authors show that some mycobacteria carrying mutations conferring resistance to two antibiotics have a higher competitive fitness than corresponding strains carrying only one of these mutations.
Addressing the Challenges of Tuberculosis: A Brief Historical Account
The historical sequence of drug development and use in the fight against TB, with a particular emphasis on the decades between World War II and the dawn of the twenty first century (2000), is summarized.
for Treatment of Tuberculosis Action of AZD 5847 , a Novel Oxazolidinone Bactericidal Activity and Mechanism of
Published Ahead of Print 4 November 2013. 10.1128/AAC.01903-13. 2014, 58(1):495. DOI: Antimicrob. Agents Chemother. Butler and V. K. Sambandamurthy Ramachandran, M. Balganesh, L. Wright, D. Melnick,


Innovative trial designs are practical solutions for improving the treatment of tuberculosis.
The multi-arm multi-stage trial design is an example of a treatment selection-adaptive design where multiple experimental arms are each simultaneously compared with a common control and interim analyses allow for poor performing arms to be dropped early.
2011 update
  • WHO website [online], publications/2011/9789241501583_eng.pdf
  • 2012