Antibiotics better in pairs.

Many types of infectious bacteria, once easily killed by a course of penicil- lin, have become resistant to even the best antibiotics. They are already beginning to break through the last line of defense, the relatively new drug vancomycin. In intensive-care units, about 15 percent of some bacterial infections are vancomycin-resistant, according to the Centers for Disease Control and Prevention in Atlanta.

Researchers are now exploring a way to fortify this defense. A new study shows that two vancomycin molecules connected together have an enhanced ability to kill antibiotic-resistant bacteria. The report by Uma N. Sundram and John H. Griffin of Stanford University and Thalia I. Nicas of Lilly Research Laboratories in Indianapolis appears in the Dec. 25 Journal of the American Chemical Society.

Eight years ago, Dudley H. Williams and his colleagues at the University of Cambridge in England discovered that molecules similar to vancomycin could easily pair up with each other, forming what are known as dimers. They sub- sequently demonstrated that dimers are more effective antibiotics than single molecules. Vancomycin, however, "is pretty lousy" when it comes to pairing with itself, Griffin says.

To overcome this weakness, Griffin and his colleagues linked two vancomycin molecules using different chemical bridges. The dimers destroyed van- comycin-resistant bacteria much better than single vancomycin units. Vancomycin works by binding to a specific piece of protein, preventing it from incorporating into the bacterial cell wall. "A dimer allows simultaneous delivery of two antibiotic molecules to the surface of a bacterium," says Williams, thus making it easier for the vancomycin to bind to the correct piece of protein.

What's puzzling, Griffin says, is that the dimers don't seem to have enhanced antibiotic activity against bacteria that normally succumb to vancomycin.

Looking more closely at how the dimer binds to the bacterial protein could help explain why, he adds.