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Review
. 2013 Sep;21(9):493-501.
doi: 10.1016/j.tim.2013.05.002. Epub 2013 Jun 11.

Rising to the challenge: new therapies for tuberculosis

Emily B Wong  1 , Keira A Cohen, William R Bishai
Affiliations
Review

Rising to the challenge: new therapies for tuberculosis

Emily B Wong et al. Trends Microbiol. 2013 Sep.

Abstract

The standard treatment for tuberculosis (TB) is lengthy, complex, and significantly toxic. Drug development for TB has stagnated for decades, but in recent years renewed commitment and coordinated research has generated a modest pipeline of new drugs that hold the potential to make treatment more effective, shorter, less complex, and less toxic in the near future. With a particular focus on bedaquiline (TMC207), the first anti-TB drug of a novel class to be approved by the US Food and Drug Administration (FDA) in 40 years, this review summarizes the recent evidence behind new developments in TB treatment. Novel drug classes, repurposed drugs, and host-directed therapies are reviewed. In parallel to these exciting developments in drug discovery, we propose that it is crucial to develop more rapid and comprehensive diagnostics that will allow the timely selection of the best regimen for individual patients.

Keywords: PA-824; bedaquiline; clofazimine; delamanid; oxazolidinones; tuberculosis.

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Conflict of interest statement

Conflict of Interest

The authors declare no conflict of interest

Figures

Figure 1
Figure 1. Chronology of TB drug discovery
TB drug discovery flourished in the mid 20th Century. Drugs appear alongside their date of discovery. Red: drugs that are FDA- approved for use in TB. Black: drugs that are FDA-approved for other uses. Blue: drugs not yet FDA-approved. Timeline adapted from [76].
Figure 2
Figure 2. Multiple agents are currently being investigated for use in TB
While many compounds are in the initial discovery phase, other drugs have begun pre-clinical or clinical development in the form of Phase 1, 2 or 3 clinical trials. Reprinted from Stop TB Partnership, working group for new TB drugs (www.newtbdrugs.org).
Figure 3
Figure 3. PA-824-pyrazinamide-moxifloxacin (PaMZ) outperforms standard
treatment in a human 14-day early bactericidal activity (EBA) study. The combination of PaMZ appears to have a synergy that produces superior reduction of viable bacterial count in sputum compared to standard therapy four-drug therapy (rifampin-isoniazid-pyrazinamide-ethambutol, RHZE) and other bedaquiline-containing combinations. Figure from [28].
See this image and copyright information in PMC

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