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Everybody’s Responsibility

As one antibiotic after another loses ground to a new resistant strain of bacteria, government officials and scientists from industry, academia, and professional scientific and medical organizations have met to examine the problem and discuss what can be done. New alliances and partnerships are forming among public health departments and scientists based at universities, and between giant pharmaceutical companies and small biotechnology firms. Now the question is: Can we beat antibiotic resistance?

The answer involves almost everybody. Drug manufacturers are one significant part of the solution.

Pharmaceutical and biotech firms are placing in the pipeline many potential new drugs intended to help meet the challenge of resistant bacteria. One is a class of antibiotics known as everninomicin that the Schering-Plough Research Institute is developing. George Miller is glad his company hung on to a soil organism called Micromonspora carbonacea, which was shown to have antibiotic activity nearly 20
years ago. From 1979 to 1984 company researchers worked with the organism and found it could make an antibiotic that was not toxic and was active against a range of disease-causing microbes known as gram-positive bacteria. But the scientists quit working on it, Miller says, because in the ’80s there was no need for a new antibiotic of this type.

In 1990, when they noticed that some gram-positive bacteria were beginning to develop resistance to existing drugs, Schering-Plough scientists plucked the organism from its home in the freezer and started back to work on it. Everninomicin contains seven different sugars that are not involved in any class of medicine used in people, Miller says. This means that no current form of drug resistance can transfer to
the new antibiotic, which in lab and animal studies has killed resistant strains of staphylococci, streptococci, and enterococci, three of the most problematic bacteria. Miller points out, however, that “resistance will probably happen to all new drugs eventually.”

Clinical trials of the first everninomicin drug have begun in South Africa and Latin America. And they may start soon in the United States, Miller says. If those trials succeed, the FDA may take another two to three years to approve the drug, he adds.

Even sooner than that, another new class of antibiotics-the oxazolidinones-may be ready for use, courtesy of Pharmacia & Upjohn, Inc. Scientists at E. I. Du Pont de Nemours actually discovered oxazolidinones more than 10 years ago but couldn’t overcome a toxicity problem with the compound, so they stopped trying to develop it into a usable antibiotic. Gary Zurenko, a senior research scientist at Pharmacia & Upjohn, was sitting in a scientific meeting in New York in 1987 when Du Pont researchers described the product. Zurenko was intrigued by its unique mechanism of action, which unlike other inhibitors stops the initiation of protein synthesis in bacteria. This was significant because its way of preventing protein synthesis in bacteria implied that “organisms resistant to the known protein-synthesis inhibitors would likely not be resistant to the oxazolidinones,” Zurenko explains. The compound also looked attractive as a drug candidate because it could be given by mouth as well as intravenously.

Over time, Pharmacia & Upjohn researchers developed a set of oxazolidinones far less toxic than the Du Pont compound. Zurenko re-ports that the first drug his group created, Linezolid, works against methicillin-resistant staphylococci, vancomycin-resistant enterococci, and penicillin-resistant streptococci and retains other key features of the early oxazolidinones. His company is now testing Linezolid on patients at several sites around the world, including in the United States.

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Tagged: Biomedicine

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