CHAPEL HILL, N.C. — Two drugs used to treat bone loss in old age may provide a new weapon against antibiotic-resistant bacteria blamed for nearly 100,000 hospital deaths across the country each year, researchers at University of North Carolina-Chapel Hill discovered.
The drugs both kill and short-circuit the "sex life" of antibiotic-resistant bacteria, opening a possible new avenue of attack against bacteria that have become increasingly resistant to common antibiotics, said Matt Redinbo, a UNC professor of chemistry, biochemistry and biophysics.
"Potentially, we have a brand new way to kill the most dangerous bacteria that are out there," said Redinbo, senior author of the study released Monday and slated for online publication in a scientific journal this week. "It's becoming harder and harder to find drugs that effectively kill bacteria in humans."
From malaria and tuberculosis to simple staph infections, stubborn bacteria pose a dangerous worldwide medical threat from infectious diseases once thought conquered by miracle drugs such as penicillin or its pharmaceutical offspring. In the United States alone, the Centers for Disease Control and Prevention estimates 1.7 million hospital patients get an infection each year, with 99,000 dying. More than 70 percent of the bacteria that cause hospital infections are resistant to at least one of the antibiotics commonly used to treat them.
As a result, patients infected with resistant bacteria have longer hospital stays and require treatment with different medicines that may be more toxic and expensive, driving up health care costs, according to a CDC report. Hospitals have also been forced to develop expensive and cumbersome protocols to combat the spread of hard-to-kill bacteria, isolating infected patients and requiring doctors and nurses to wear masks, gloves and other protective gear.
Hospital officials say they are caught in a squeeze play: More patients with stubborn infections; fewer antibiotics that are fully effective.
"The problem it creates for us in a hospital is that patients are sicker and harder to treat," said Robin Carver, interim director for infection prevention and control at WakeMed Hospital in Raleigh, N.C. "Our options keep getting smaller and smaller and smaller."
That's why researchers, while cautious not to hype the early results, are hoping for a bigger payoff from the laboratory discovery of one of Redinbo's graduate students, Scott Lujan.
"The potential for its impact is great, but more research needs to be done," said Dr. David Hecht, professor of medicine, microbiology and immunology and infectious disease division chief at Loyola University Health Systems near Chicago.
So far, University of North Carolina laboratory research on E. coli bacteria brought a hoped-for result. Two off-the-shelf bone loss drugs, clodronate and etidronate, blocked a key mechanism used to squirt genetic changes from one bad bug into another, including the gene that helps ward off an antibiotic attack.
But the research, which still has to be duplicated in animals and humans, also produced a surprise - the two drugs killed any bug that already had the antibiotic-resistant gene. The scientists aren't sure why this happened.
"We didn't expect this," said Redinbo, whose study will appear in the Proceedings of the National Academy of Sciences. "It kills the bad guys with the gun whether they're shooting it or not."
This discovery is important because a broad range of bacteria use this mechanism to pass along "genetic upgrades." The bugs not only pass this information between the same type of bacteria, but between different kinds of bacteria, exponentially increasing the problem of antibiotic resistance, Hecht said.
Hecht urges caution about the new research. What's important about the UNC discovery is the vulnerability of the bacterial mechanism for passing along genetic upgrades - not the shortcut of using two off-the-shelf bone loss drugs. He compared the mechanism to a lock-and-key set - all bacteria have the mechanism, but a different pharmaceutical key may be needed to fit the lock of a different bacteria and disrupt the sharing of genetic material.
"It's the concept that's important," Hecht said.
Most existing antibiotics attack infectious bugs by breaking down the cell wall that holds bacteria together or knocking out the "protein factory" necessary for growth and survival. But if Lujan's laboratory discovery works on other stubborn bacteria, the long-term result could be a new family of antibiotics based on a type of drug already approved for use in humans.
That could save pharmaceutical companies the massive research and development costs of bringing a brand new drug to market, said Scott Singleton, a professor in UNC's School of Pharmacy who has also been studying the problem of antibiotic-resistant bacteria.
"I think it's huge," Singleton said of Redinbo's and Lujan's research. "It's a dramatic shortcut."
This could also encourage drug companies to develop a new generation of antibiotics, helping them overcome a reluctance brought on by the thin profit margins of this kind of drug and the short window of efficacy caused by bacteria that rapidly develop resistance to new drugs.
The rapid cycle of bacteria developing resistance to antibiotics is partly a self-inflicted medical wound, said Dr. David Weber, medical director of infectious disease control at UNC Hospitals. Patients request antibiotics too often, and doctors over-prescribe.
"We just way overuse antibiotics," he said. "That's because antibiotics are just so good."
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(News researcher Denise Jones contributed to this report.)
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