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Why New Drugs Now?
Drug-Resistant TB

Drug-Resistant TB

Drug-resistant strains of tuberculosis are complicating efforts to control the global TB pandemic, and putting thousands of lives at risk.

Drug-resistant TB is the man-made result of interrupted, erratic, or inadequate TB therapy. It develops when the long, complex, decades-old TB drug regimen is poorly administered, or when patients stop taking their medicines before the disease has been fully eradicated from their body. Once a drug-resistant strain has developed, it can be transmitted directly to others just like drug-susceptible TB.

MDR-TB Multidrug-Resistant TB (MDR-TB) is defined by resistance to the two most commonly used drugs in the current four-drug (or first-line) regimen, isoniazid and rifampin. WHO treatment standards require that at least four drugs be used to treat TB to avoid the development of further resistance.

MDR-TB is not limited to the developing world. During the late 1980s and early 1990s, outbreaks of MDR-TB in North America and Europe killed more than 80% of those who contracted the disease. During a major TB outbreak in New York City in the early 1990s, one in 10 cases proved to be drug-resistant.

  Every year, an estimated 490,000 new MDR-TB cases occur. The WHO estimates that MDR-TB makes up greater than 10 percent of all new TB cases in Eastern Europe, the region most affected by the disease. Rates of up to six percent have been reported in many countries, while in some parts of the former Soviet Union, up to 22 percent of all patients with TB have resistant strains.

When first-line drugs fail, second-line drugs are used to treat MDR-TB. Unfortunately, some second-line drugs are toxic and can lead to negative side-effects. They must be taken for up to two years in order to eradicate the infection. The costs of curing MDR-TB can be staggering — as much as 1400 times that of regular treatment. Expensive treatment is often out of reach to patients who are infected with drug-resistant strains. At the same time, MDR-TB poses a significant challenge to national healthcare systems.

XDR-TB Extensively Drug-Resistant TB (XDR-TB), also known as Extremely Drug-Resistant TB, is emerging as an even more ominous threat. XDR-TB is defined as TB that is resistant to any fluoroquinolone, and at least one of three injectable second-line drugs (capreomycin, kanamycin, and amikacin), in addition to isoniazid and rifampin. This makes XDR-TB treatment extremely complicated.

In March 2006, the Centers for Disease Control (CDC) released the first known data on XDR-TB. The CDC and the WHO surveyed TB strains from a global network of TB laboratories and identified XDR-TB cases in all regions of the world. In the worst- affected areas, an average of 10 percent of MDR-TB cases were found to be XDR-TB. According to the WHO, XDR-TB remains comparatively rare. However, WHO estimates that there were almost half a million cases of MDR-TB worldwide in 2006, and MDR-TB usually has to occur before XDR-TB arises. We also know that, according to the findings from the only global study carried out so far, that in some places perhaps as many as 30% of MDR-TB cases were in fact XDR-TB, but this is likely to be uncommon. Wherever second-line drugs to treat MDR-TB are being misused, the possibility of XDR-TB exists. Research is being carried out to better understand XDR-TB, and the WHO and others have mounted an intensified global response to escalating global resistance.

So long as TB is treated with a long, complex, decades-old drug regimen, drug resistance will continue to develop. Novel TB drugs, working through new biological mechanisms of action, are designed to be effective against drug-susceptible and drug-resistant strains alike, saving lives. A shorter regimen, reliably administered, would also minimize the potential for further resistance.