Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT Southwestern researchers find clues to TB drug resistance

30.03.2010
Two new tuberculosis studies by UT Southwestern Medical Center researchers provide good news and bad news about the bacterium that infects nearly a third of the world's population and a disease that kills nearly 2 million people each year.

The good news: A type of blood pressure medication shows promise at overcoming some drug-resistant tuberculosis, at least in the laboratory. The bad news: The Mycobacterium tuberculosis bacterium, which causes the disease, might be resistant to treatment in more people than previously thought.

Dr. Tawanda Gumbo, associate professor of internal medicine at UT Southwestern and senior author of the studies, said the research challenges current thinking about how the TB bacterium works in the body as well as how best to kill it.

His published findings come after the Dallas County Department of Health and Human Services announced this month that while the number of TB cases diagnosed in Dallas County dropped to 195 in 2009 from 219 a year earlier, the county's rate of infection is still 1.5 times higher than the national rate.

In the first study, available online and in the April 15 edition of The Journal of Infectious Diseases, Dr. Gumbo and his colleagues used an experimental apparatus to simulate the way TB bacteria grow in the human lung. When they exposed the bacteria to drugs commonly used to treat the disease – ethambutol and isoniazid – the bacterial cells activated a cellular mechanism that pumps each drug out of the cells. The pumping action enables the rapid emergence of high-level resistance to the drugs whether administered together as well as individually, Dr. Gumbo said.

"We treat TB with multiple drugs essentially to protect each other from resistance, but yet we've been puzzled with why you find resistance to both drugs together," Dr. Gumbo said. "Our findings make sense – it is more efficient from the bacteria's viewpoint to employ the same mechanism get rid of multiple attackers, whether they strike alone or at the same time."

Resistance was drastically reduced, however, when the researchers gave the blood-pressure drug reserpine – which is known to block this pumping action – to the TB cells before administering ethambutol and isoniazid.

"There is already a known solution to this problem," Dr. Gumbo said. "Hopefully now we can reduce resistance to TB treatment drugs."

Current TB treatment uses multiple drugs simultaneously, in hopes of preventing drug resistance. The next step in his research, Dr. Gumbo said, is to test all the first-line drug treatments together with the pump blocker in humans.

If first-line drugs won't work to kill TB, the person is said to have multidrug-resistant TB and doctors proceed to second-line treatments, which are usually more expensive and more toxic and take longer to work, Dr. Gumbo said.

In Dr. Gumbo's second study, available online and in the April edition of Antimicrobial Agents and Chemotherapy, the researchers found that more people might harbor drug-resistant TB than currently believed because tests that detect the TB bacteria's resistance don't account for variations in height, weight and other factors among TB patients.

Guidelines for testing whether a person is infected with a drug-resistant TB strain were developed more than 40 years ago. They involve determining the lowest concentration of a drug that will kill at least 95 percent of the TB bacteria in a patient. The TB is said to be resistant to the drug if more than 1 percent of TB still grows at that concentration.

Dr. Gumbo said those guidelines are useful for showing trends, but are not effective for predicting how an individual will respond to therapy. Recommended drug concentrations and dosages, for example, don't account for factors such as body weight, height, race and how much food a person ate before being tested.

"Science has evolved," Dr. Gumbo said. "We have better tools now so we can do more and predict better treatment."

In the second study, he again simulated TB in the human lung and virtually simulated eight clinical trials involving 10,000 patients. The computer simulation factored in pharmacokinetics (how a body handles a drug based on heterogeneous factors) to determine how likely a dose of a given drug is to kill TB.

Dr. Gumbo's research team found that the concentrations typically used in practice are too low, leading people to think they have treatable TB, when in fact their disease might be resistant to common drugs.

"There is likely more multidrug-resistant TB than previously thought – possibly up to four times as much," Dr. Gumbo said. "That means some people may be getting underdosed with medicine weaker than the disease, and they die."

The next step, Dr. Gumbo said, is to confirm these computer-driven results in patients.

Dr. Gumbo's research is funded by a 2007 National Institutes of Health Director's New Innovator Award, which supports bold ideas from some of the nation's most innovative early-career scientists.

Other UT Southwestern researchers participating in the research were Sandirai Musuka, research associate in internal medicine, and Dr. Shashikant Srivastava, postdoctoral researcher in internal medicine. Researchers from Texas Tech University Health Sciences Center's School of Pharmacy also were involved in the study published in The Journal of Infectious Diseases.

Visit http://www.utsouthwestern.org/infectiousdiseases to learn more about UT Southwestern's clinical services for infectious diseases, including tuberculosis.

This news release is available on our World Wide Web home page at http://www.utsouthwestern.edu/home/news/index.html

To automatically receive news releases from UT Southwestern via e-mail, subscribe at www.utsouthwestern.edu/receivenews

Kristen Holland Shear | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Studies and Analyses:

nachricht Obstructing the ‘inner eye’
07.07.2017 | Friedrich-Schiller-Universität Jena

nachricht Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>