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Med disables drug-resistant tuberculosis in lab. Will it work in humans?

Curing tuberculosis that's resistant to the most commonly used, first-line drugs is a growing problem, with an estimated half million people worldwide now infected with so-called MDR (multi-drug resistant) TB. Of those, an estimated 50,000 have extensively drug-resistant (XDR) strains that don't respond to more potent drugs, either. Now scientists say they've hit upon a potential breakthrough: an antibiotic previously dismissed as useless against TB killed 13 resistant strains of the bacteria in the lab when it was combined with another drug.

The finding, published today in Science, has yet to be tested in people, study co-author John Blanchard, a biochemistry professor at Albert Einstein College of Medicine in New York, tells ScientificAmerican.com. But in a Petri dish, the meds, meropenem and clavulanate, destroyed and stopped the replication of the resistant TB bacteria, cultured from mucus samples from South Korean patients.

Mario Raviglione, director of the World Health Organization's Stop TB department, called the study "quite promising."

"This is something I would consider of great usefulness in this era when we're all desperate to find new treatments for MDR and XDR, specifically," Raviglione, who was not involved in the study, told ScientificAmerican.com. "Their use should be studied as soon as possible," he said. "It would be a major achievement" if the meds prove effective in people.

Meropenem is from a class of medicines called beta-lactam antibiotics, which includes penicillin. Beta-lactams had been tried against TB before, Blanchard says, but didn't appear to work. "That's why it's a little startling that an old class of antibiotics have emerged as effective against TB," he says.

It may have been a matter of finding an effective combination, he notes. Clavulanate inhibits an enzyme called beta-lactamase that normally prevents the penicillin-like antibiotics from destroying TB. Meropenem blocks that same enzyme, as well as others that allow TB to grow. Previous research indicates that the compounds may kill TB by causing the bacteria's cell walls to rupture.

Nearly nine million people worldwide are infected with tuberculosis, and about two million of them die annually, according to the Centers for Disease Control and Prevention (CDC). The infection causes weight loss, coughing, chest pain, night sweats, fever and fatigue. Most cases of MDR-TB have been diagnosed in China and the former Soviet bloc, and there were 98 cases reported in the U.S. in 2007.  XDR strains have been found in 41 countries, including the U.S., where there were 83 cases recorded by the CDC between 1993 and 2007. TB is particularly deadly in patients with HIV – the virus that causes AIDS – who have weakened immune systems and, so, are more susceptible to the disease and, also, have a harder time fighting it.

Both meropenem and clavulanate are already approved by the Food and Drug Administration (FDA) to treat severe infections such as E. coli and spinal meningitis, Blanchard says. Clinical trials in XDR-TB patients are planned in South Korea and South Africa.

For more, check out our in-depth report on what's being done to fight multi-drug resistant TB.

Image of Ethiopian TB patient/World Health Organization

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