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Times of India
3 March 2009
By Kounteya Sinha
New Delhi, India

The world’s most dangerous tuberculosis strain – the extremely drug resistant (XDR) TB – has finally been slain, but only in the lab.

American scientists have found that a combination of two FDA–approved drugs Clavulanate and Meropenem, meant for fighting other bacterial infections like ecoli, completely blocked the growth of 13 strains of XDR TB, isolated in the lab.

According to scientists from Albert Einstein College of Medicine in New York and National Institute of Allergy and Infectious Diseases (NIAID), the drugs worked in tandem – while one brought down the guard of the TB bacteria by inhibiting the enzyme that normally shields it from antibiotics, the other killed it.

Phase II clinical trials on humans are now being planned simultaneously in South Korea and South Africa.

Scientists have reported their breakthrough in the latest issue of the ‘Science’ journal.

Speaking to TOI, Dr John Blanchard, professor of biochemistry at Einstein and senior author of the paper, said that in the lab, scientists successfully killed all XDR TB bacteria in less than two weeks time.

Dr Blanchard said, “The entire discovery happened by chance. We didn’t set out to see whether these two drugs, alone or in combination, fought TB. Now, after three years of lab research, Clavulanate was found to be highly effective in inhibiting the crucial enzyme that shields TB bacteria while Meropenem was highly effective in killing the TB organism completely.” He added, “Normally, it takes two years of continuous therapy to treat drug resistant TB strains. If this combination works in humans, we will be able to completely eliminate the organism within two weeks time.”

Over one–third of the world’s population is infected with TB which claims 1.5 million lives every year globally.

More TB patients are becoming multi–drug resistant (MDR), meaning they don’t respond to the two antibiotics most commonly used against TB.

XDR TB is the most dangerous and is resistant to at least four of the drugs used. Without therapy, death rates in XDR–TB are as high as 100%.

Recently, scientists in India said XDR had been detected in the country and could account for 8% of those suffering from MDR TB. The team examined 3,904 lab samples and found 1,274 were positive for TB. Of these, 32% were multiple drug resistant (MDR–TB), of which 8% were XDR–TB cases.

Mortality rate of XDR–TB patients in the study was as high as 42%. What’s worse, majority of patients with XDR–TB were below 30 years.

"This discovery could be one of the most promising developments in TB research since the discovery of isoniazid," said William Jacobs, professor of microbiology at Einstein.

NIAID researcher Clifton Barry is launching a clinical study of the drug combination in South Korea by the end of 2009 involving approximately 100 TB patients. Additionally, Einstein College of Medicine and the Nelson Mandela School of Medicine in Durban, South Africa are starting a separate trial slated for 2009 that will test the potency of the drug combination in a smaller number of TB patients.

If the results are successful, a trial involving thousands of XDR–TB patients will be conducted.

TB is the single largest killer of AIDS patients in India – over 60% of all AIDS patients contract and ultimately die of TB.

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