Treatment of multidrug-resistant and extensively drug-resistant tuberculosis: current status and future prospects

Abstract

Drug resistance in Mycobacterium tuberculosis arises from the man-made selection of mutants that result from spontaneous chromosomal alterations. Preventing the development of drug-resistant TB through a good control program based on directly observed treatment, short-course, is of paramount importance. Established multidrug-resistant (MDR)-TB requires alternative specific chemotherapy, comprising drugs with higher cost and greater toxicity delivered on a programmatic basis. The development of new anti-TB drugs would help to prevent and treat MDR-TB. Notably, moxifloxacin and gatifloxacin are being tested for shortening treatment in Phase III trials, while three novel compounds, TMC-207, OPC-67683 and PA-824 are in Phase II studies for both drug-susceptible and drug-resistant disease. The roles of surgery and immunotherapy in the management of MDR-TB require further evaluation. The recent emergence of extensively drug-resistant TB poses a serious challenge to the global control of TB. In order to combat extensively drug-resistant TB, strengthening of directly observed treatment, short-course and drug-resistance programs, alongside other strategies, including the development of newer diagnostics and drugs, is mandatory.

Keywords::

• drug resistant
• fluoroquinolone
• new drugs
• treatment
• tuberculosis

Acknowledgements

We would like to thank AM Ginsberg for her kindness in providing the preliminary results of Phase IIa extended EBA study on PA-824 through personal communication.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.