Drug Pipeline To Fight Antibiotic Resistance Is Running Low : Shots - Health News Infectious disease specialists debate whether it's better to give the strongest antibiotics all at once for drug-resistant germs or save the most innovative medicines for use as a last resort.

How Best To Use The Few New Drugs To Treat Antibiotic-Resistant Germs?

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The Centers for Disease Control and Prevention is expected to issue a warning today. Antibiotics are more frequently failing to kill germs. Millions of people are at risk. Tens of thousands of Americans die every year as a result. Now scientists are fighting back using the principles of evolution. Here's NPR's science correspondent Richard Harris.

RICHARD HARRIS, BYLINE: The usual response to these antibiotic-resistant germs is to look for new drugs. But this perpetual arms race between bacteria and drug developers is problematic. For one thing, it costs a lot to develop these new drugs, and they don't usually pay for themselves. At a meeting last week in Washington, D.C., industry officials were bemoaning that one pioneering company recently went bankrupt as a result.

GREG FRANK: Their sales were nowhere near enough to recoup just their operating costs, let alone their investment expenditures. And we're seeing that time and time again with other companies.

HARRIS: That's Greg Frank at an industry group called the Biotechnology Innovation Organization. He says it's not only a crisis for the industry, but for public health.

FRANK: We're not developing nearly enough products to stay ahead of resistance, and many of those aren't going to reach the market. Those that do are right now destined to fail. And so the very dry pipeline is only going to get worse.

HARRIS: The industry is trying to convince the federal government to provide big-dollar incentives to keep this enterprise afloat. But Andrew Read at Penn State University argues there must be a better way to fight these superbugs other than engaging in an endless arms race with them.

ANDREW READ: Most people are looking for new drugs or new drug targets or rapid diagnostics, that sort of thing. And all that is important work. But the heart of the problem is the evolutionary process that generates the resistance.

HARRIS: And few scientists are focusing on that most basic problem to find out-of-the-box solutions. He is an exception. One idea? Since bacteria are more likely to evolve resistance if they are exposed to antibiotics for a long time, why not try limiting the dose, at least for people with healthy immune systems?

READ: Oftentimes, in many situations, the immune system kicks in, and it kills the bugs and clears them out. So all the drugs need to do is buy the immune system a little time. So that's the most obvious situation where we don't need the drugs to finish off every last bug. We just need the drugs to make us healthy again and let our immune systems take care of us.

HARRIS: Another idea is to hit germs with several drugs at once, the way tuberculosis is treated.

READ: Psychologically, it's a bit scary putting all of your firepower into one regimen. On the other hand, it can work very effectively at preventing the evolution of resistance. And so instead of just using drug A, and that fails, and then drug B, and that fails, and then drug C, using A, B and C altogether can stop any of them failing.

HARRIS: Another evolutionary biologist working in this area is Hinrich Schulenburg in Kiel, Germany.

HINRICH SCHULENBURG: One idea that we are particularly interested in is sequential therapy.

HARRIS: That is giving different antibiotics in rapid sequence, say, switching every 12 or 24 hours so the environment for the germ is always changing.

SCHULENBURG: And we know from evolutionary theory that this makes it very difficult to any organism to adapt fast to these conditions.

HARRIS: He's tested that idea successfully in petri dishes and is now gearing up to test the concept in humans.

SCHULENBURG: The point that we as evolutionary biologists want to make is that whatever kind of treatment we design, we need to take into account how bacteria evolve.

HARRIS: One of these nontraditional ideas came up at the meeting in Washington, D.C., last week. Sheila Connelly is VP of research at a small company called Synthetic Biologics in Maryland. They're developing a counterintuitive drug, an enzyme that actually destroys common antibiotics like penicillin. The idea is to give these anti-antibiotic pills to people who are getting the antibiotics injected directly into the bloodstream.

SHEILA CONNELLY: And our enzyme stays in the gut. And it's not absorbed into the blood, so it doesn't affect antibiotic efficacy.

HARRIS: But it does destroy antibiotics in the gut. And that's where they are most likely to trigger drug resistance.

CONNELLY: So if we can avoid the gut being exposed to antibiotics, then we prevent the evolution and emergence of antibiotic resistance.

HARRIS: Preliminary findings from people suggest that it works. And it also reduces the risk that people will develop a potentially deadly infection called C. difficile, which is triggered by antibiotics in the gut. Industry spokesman Greg Frank agrees there is a role for novel approaches.

FRANK: I do think that there can be some creative ways to buy us time. I am firmly of the opinion, though, that we will almost certainly never outthink bacteria with our current arsenal. We'll always need to be developing new medicines.

HARRIS: So he and his associates are lobbying Congress to pass a bill that will pay companies to keep innovating even if their products end up largely sitting in reserve, waiting for the day when they are needed most. Richard Harris, NPR News.

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