Breathtaking discovery? TB hospitals like this one in Guatemala are seeing more and more patients with drug-resistant strains and badly need new options.
Malcolm Linton
Thanks to a barroom conversation researchers may have stumbled on a combination of powerful drugs to combat drug-resistant tuberculosis (TB), a threat increasing throughout the world. New research suggests that meropenem and clavulanate, both of which are approved by the Food and Drug Administration of the United States to fight against bacterial infections, tame some of the most virulent strains of tuberculosis.
An increasing number of people have multidrug-resistant (MDR) strains of Mycobacterium tuberculosis , which causes tuberculosis. Last year, the World Health Organization has reported the largest number of cases ever - about half a million - and highlighted the countries of the former Soviet Union and China as the hardest hit. Currently the MDR-TB patients have to take expensive treatments highly toxic for as long as 2 years to cure their infections. And since 06, the researchers found that nearly 10% of these people have actually (XDR) strains "extensively drug-resistant" that can Outsmart almost all known treatments. MDR-TB has a rate of more than 50% mortality, and XDR-TB is lethal yet -. Especially when combined with HIV infection, a serious problem in several countries in southern Africa
But in today's issue of science , a group headed by biochemist John Blanchard of the Albert Einstein College of Medicine in New York reported the test tube evidence that, when used in tandem, meropenem and clavulanate worked against the 13 XDR-TB strains they tested. Although some researchers have expressed surprise that Science accepted an in vitro study of drug without animal or human data, Blanchard stressed that the urgency of the problem and the availability of these drugs raises important their results.
Blanchard said the idea goes back to a meeting he had in a Paris bar 3 years ago with a French student graduate, Jean-Emmanel Hugonnet, who wanted to work in his laboratory on issues fundamental to enzyme kinetics. "It was not designed as a drug discovery program," says Blanchard. Hugonnet had worked in a laboratory in Paris with the β-lactamase enzyme, which is made by M. tuberculosis and other bacteria and has a function disorder, and they decided to make that the center of his studies the enzyme is important because it paralyzes a class of antibiotics called beta-lactams, including penicillin and called meropenem. newer drug that is commonly used to treat pneumonia and meningitis.
But if there was a way to inhibit β-lactamase so that drugs like meropenem could work their magic? Blanchard knew a former drug called clavulanate, which stops the enzyme was used just this way to help amoxicillin β-lactam antibiotics treat all ear pain urinary tract infections. (Indeed, an earlier study in patients with this combo of tuberculosis showed that it had some activity against the virus.) So he and his colleagues decided to combine clavulanate with various beta-lactam antibiotics and tested against various M. tuberculosis strains. "Once you hit on β-lactamase chemically, bam, these other compounds have effects," says Blanchard. The combination of clavulanate and meropenem made the best team reports, with tiny concentrations of β-lactam killing all M. tuberculosis culture of the team tested.
"I'm very excited about it," said microbiologist Willem Sturm of the Nelson Mandela School of medicine at Durban, South Africa, which recently faced a major outbreak of XDR-TB there. "But we really need to see if they do that in vitro experiments promise." to that end, Sturm hopes to launch a clinical study in South Africa later this year with Brian Currie, an infectious disease doctor at Albert Einstein. the study will test the drug in people who are co-infected with HIV and MDR or XDR strains Mr. TB . infectious National Institute researchers allergies and diseases of the United States also have plans for a second test with colleagues in South Korea to test antibiotics for tuberculosis patients resistant drugs that are not infected by HIV.
Some other compounds to fight against XDR-TB are in clinical trials, but they have yet to pass security barriers - let alone evidence of efficacy - that meropenem and clavulanate have already cleared. According to the Global Alliance for TB Drug Development, none of these studies is likely to be completed until at least 2012.
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