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Researchers are taking a phoenixlike approach in developing new antibiotics that self-destruct or regenerate as a way of combating growing problems with drug resistance.
One of the drugs is a modified aminoglycoside antibiotic. Normally, the drug is inactivated when bacteria attach an inhibitory group to its chemical structure. The modified version accepts the inhibitory group but then detaches it a short time later. In effect, the drug regenerates its active form to remain effective in fighting bacteria and to discourage the development of bacterial resistance enzymes. "The common mechanism of resistance is not effective against this drug," said Shahriar Mobashery, PhD, professor of chemistry at Wayne State University in Detroit. A report on the research appeared December 22, 1999, in the Journal of the American Chemical Society.
The other drug is a modified version of cephalosporin that self-destructs when exposed to light outside the body. This feature may help fight drug resistance because most antibiotics are not highly metabolized in the body and, when eliminated, continue to select for resistant bacteria in sewers and other environments. "The lingering presence of antibiotics has provided increased opportunities for bacteria to develop resistance to them in these environments," said Mobashery.
Neither strategy has been tested yet in animals or humans. A report on the light-sensitive drug is in the January 13 Journal of Medicinal Chemistry.
Voelker R. Fighting Antibiotic Resistance. JAMA. 2000;283(4):470. doi:10.1001/jama.283.4.470-JQU90012-3-1
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