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TB Strain Thrives on Antibiotic

By Kristi Birch

Most cases of tuberculosis can be cured, but 2 million people still die every year. The emergence of HIV created a population especially susceptible to TB infection. Moreover, multidrug-resistant TB, which typically emerges when people don’t complete their months-long course of antibiotics, has become a serious public health problem. And now researchers have documented a case of TB that is not only resistant to an antibiotic used to treat it, but actually thrives on it.

Working with his colleagues in China, Ying Zhang, MD, PhD, professor in the W. Harry Feinstone Department of Molecular Microbiology and Immunology, has, for the first time, documented a case of TB that is nourished by the antibiotic Rifampicin (RIF), an important drug used to treat TB. “It stimulates the growth of the bacteria,” says Zhang. “That’s scary.”

RIF-dependent TB bacteria was first found in 1990 in Japan but has since rarely been reported, and there has been no case study examining such a patient’s response to treatment containing RIF. So when Zhang’s colleagues at Chongqing Pulmonary Hospital in China discovered these RIF-dependent bacteria in the lab, Zhang decided that they should do a study of the infected patient—and characterize the TB bacteria in terms of genetic mutations involved in RIF resistance. Their study appears in the January 2010 issue of The International Journal of Tuberculosis and Lung Disease.

The standard initial treatment for a patient with TB is four different antibiotics, one of which is RIF, taken daily for six months. The Chinese patient, a 35-year-old man, was given the WHO-optional thrice-weekly regimen. Two and a half months into his treatment, his symptoms worsened, and he began the retreatment regimen—which also contains RIF. When the bacteria were isolated from the patient and a drug-sensitivity test was conducted, the researchers found that the bacteria grew better in the presence of RIF. They then switched to the more powerful Rifapentine, along with other second-line drugs, but the patient actually got worse. However, when they removed any RIF-related drug from the patient’s treatment regimen, he got better. Two years later, he remains TB-free.

Zhang says that this tuberculosis bacillus seems to have some unique mechanism that makes it especially virulent. But what it is, and how this TB strain progressed from ignoring the drug to feeding off it, is a mystery. “We still don’t understand the mechanism,” says Zhang. “We don’t know how this dependence occurs.”

Simply banning RIF is not feasible because it is an important frontline drug used in treating TB. The frequency of RIF-dependent TB strains is not yet known, although based on the preliminary study of the collaborators in China, about 6 percent to 10 percent of all TB isolates (bacterial strains isolated from individual patients) are RIF-dependent.

“We want to know how infectious these strains are,” says Zhang. “If such RIF-dependent strains are highly transmissible, it would be very worrying.