UF Research Suggests Antibiotic Combination Could Beat Bacterial "Superbugs"

May 29, 2003

GAINESVILLE, Fla. — Deadly drug-resistant bacterial infections that endanger hospital patients often leave doctors with few treatment options, but University of Florida researchers report the combination of a promising new antibiotic and an older, less-used drug could provide another weapon against the “superbugs.”

In laboratory studies, UF researchers found small amounts of the new antibiotic, daptomycin, could kill more than 100 times as many drug-resistant Staphylococcus aureus bacteria when combined with the antibiotic oxacillin, which has lost much of its effectiveness against the bacteria, said Dr. Kenneth H. Rand, a professor of pathology, immunology and laboratory medicine at UF’s College of Medicine.

Staphylococcus aureus bacteria, also known as staph, can overcome drugs when tougher strains survive and multiply, Rand said. Thousands of drug-resistant staph strains are believed to exist, about half of them resistant to oxacillin.

Officials with the federal Centers for Disease Control and Prevention estimate that drug-resistant staph infections may strike as many as 100,000 Americans each year, most of whom contract the infections in hospitals. In recent years, only the drug vancomycin has been widely successful at eradicating the infections, and researchers – fearing the bacteria will grow resistant to vancomycin as well – have been racing to find new alternatives.

“The potential for these strains of staphylococcus to become resistant to everything is very real,” Rand said. “In 2002 there were two (vancomycin-resistant) strains found in the United States, both of which were fortunately contained through vigorous infection-control efforts and didn’t spread. But they could have.”

UF researchers tested 18 strains of drug-resistant staph bacteria, said Rand, who presented the findings last week at the American Society for Microbiology’s 103rd General Meeting in Washington, D.C. He said all were found to be susceptible to daptomycin but resistant to oxacillin.

The scientists used small amounts of daptomycin, often less than what’s needed to completely halt growth of the bacteria, Rand said. By measuring the number of bacteria killed after exposure to various concentrations of daptomycin, they determined that one-half or one-quarter the amount needed to completely halt growth was far more effective when supplemented with a fixed amount of oxacillin – the drug combination killed more than 100 times as many bacteria in 24 hours as the same amount of daptomycin alone.

“In combination with daptomycin, the oxacillin becomes a useful drug again, so it’s almost like a rejuvenation,” he said.

Next, Rand hopes to learn how the two drugs interact to provide their enhanced effect against cultures of staph bacteria. The UF study was funded by a $24,000 grant from daptomycin manufacturer Cubist Pharmaceuticals.

Staph bacteria colonize human skin and mucus membranes and can cause infections ranging from pimples to potentially life-threatening bloodstream infections, according to the CDC.

Until the mid-1980s, drug-resistant Staphylococcus aureus bacteria were almost nonexistent, but today they cause 30 percent to 60 percent of all staph infections and pose a significant problem in health-care facilities, Rand said. These infections mainly strike patients who are elderly or very ill, or who have open wounds or catheters providing entry to the bloodstream, according to the CDC. Drug-resistant strains of bacteria are popularly called superbugs.

Daptomycin now is available only to researchers, but the federal Food and Drug Administration is reviewing it for commercial sale, he said. If approved by the FDA, it’s likely the drug would first be used by itself against drug-resistant staph infections, so physicians could learn about its usefulness without other drugs complicating their observations.

Rand cautioned that no animal or human studies have been conducted to show the effectiveness of the daptomycin-oxacillin combination. But physicians might choose to use it, particularly if an infection couldn’t be controlled with daptomycin alone.

“It’s not something the public should be looking forward to as the be-all and the end-all that’s going to cure everybody, but it does provide a potential improvement in treatment,” he said.

For most infections, daptomycin should be a sufficient treatment because the drug is so powerful, said Michael Rybak, a professor of pharmacy and medicine and director of the Anti-Infective Research Laboratory at Wayne State University’s Eugene Applebaum College of Pharmacy and Health Sciences in Detroit who also is studying daptomycin. Clinical trials would be needed to prove the combination is more effective than daptomycin alone, he said.

“We haven’t been able to improve daptomycin activity by combining it with other drugs when it is used in concentrations that will be given to patients,” he said, adding that his team’s research has involved amounts of daptomycin sufficient to kill 100 percent of bacteria in cultures tested.

Researchers don’t know why small amounts of daptomycin work better against drug-resistant staph bacteria when combined with oxacillin, Rand said, but he plans to investigate.

“We need to know because it will help us in our understanding and thereby help us predict whether the combination will be useful in the long term,” he said.