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The pipeline for antibiotic resistance drugs is low: shots



The bacteria Pseudomonas aeruginosa – the bacteria in the form of sticks in this toned, scanning electron microscopic image ̵

1; are found in soil, water and normal flora in the human intestine. But they can cause serious infections of wounds, lungs, skin and urinary tract and many strains of pseudomonas are drug resistant.



Library of Scientific Photography / Source of Science


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Library of Scientific Images / Source of Science

Pseudomonas aeruginosa bacteria – bacteria in the form of sticks in this toned, scanning electron microscopic image – are found in soil, water and normal flora in the human intestine. But they can cause serious infections of wounds, lungs, skin and urinary tract and many strains of pseudomonas are drug resistant.



Library of Scientific Photography / Scientific Source

Five years ago, Mary Millard went to the hospital for heart surgery. A dirty medical instrument gave her an infection that led to septic shock. Her heart was struggling, and her lungs and kidneys were failing.

"What I caught was a pseudomonas and a very viral superbook," says the 60-year-old former nurse who lives in Baton Rouge, La., This bacterium. no longer responds to most antibiotics and "she lives in you all the time so I'm antibiotics for life," she says.

Her doctor prescribed her one of the most powerful antibiotics available, and there is no clear reserve for her if it stops working. "It's kind of a wait and see. And it's scary."

Millard is just one of about 2 million Americans who have been infected with a super bug. Tens of thousands die every year, and their numbers are significantly higher worldwide.

This week, the Centers for Disease Control and Prevention is expected to publish a new major report to update these figures and provide a progress report in efforts to combat antibiotic resistance.

People in the business of inventing new drugs do not need to be told one of the most disturbing facts: It just doesn't make much financial sense for companies to develop new antibiotics.

Medications are used for short-term treatment, unlike those that patients can take a lifetime to deal with a chronic illness. And the most innovative antibiotics are kept on the shelf to minimize the development of resistance.

Yet, bacteria are constantly evolving to outsmart the current crop of drugs, so new antibiotics are needed all the time. Achaogen has managed to bring one to the market recently, but as doctors (reasonably) only reserve it for the most desperate cases, the product was hardly sold.

"Their sales were not enough to offset their operating costs alone, let alone their investment costs," says Greg Frank of the Biotechnology Innovation Organization, an industry group. "And we see this time and again with other companies."

He says that this is not only a crisis for the industry but also for public health.

"We don't develop nearly enough products to stay ahead," he says. Frank counts only 70 products at various stages of development. "Many will not reach the market," he says. who do so are destined to fail "for economic reasons." And so the dry pipeline will only get worse. "

The industry is trying to persuade the federal government to provide big-dollar incentives to keep the flow of antibiotics going. (A bill called the Prohibition Act is about to be Kon Greens.)

But Andrew Reed, a biologist at Penn University, argues that there must be a better way to combat these super-gods than to participate in an endless arms race with them.

"Most people seek new drugs or new drug targets or quick diagnosis "- tests that can quickly help doctors identify the best antibiotic for an infection, he says." And all this is important work, but the core of the problem is the evolutionary process that generates resistance. "

Few scientists focus arhu this most fundamental problem to find solutions that are not available. He is an exception.

One idea: Since bacteria are more likely to develop resistance if exposed to antibiotics for a long time, why not try to limit the dose, at least for people with a healthy immune system?

"Often in many situations the immune system invades and it kills bugs and clears them," Read says. "So all the medicine we have to do is buy the immune system a little while. So this is the most obvious situation where we don't need drugs to finish every last glitch. We just need the drugs to make us healthy again and let our immune system take care of us. "

This idea must be tested in humans. Read the notes that many of these current antibiotic prescribing rules are based on tests done long ago. Efforts to improve these practices are based primarily on health outcomes rather than consideration of antibiotic resistance.

Another idea is to hit germs with several drugs at once, the way to treat tuberculosis with a multidrug combination. (Resistance still occurs with tuberculosis, but to a large extent when people are unable to continue their medication.)

"It's psychologically a little scary to put all your firepower into one mode," read admits. "On the other hand, it can work very effectively to prevent the evolution of resistance. So instead of just using drug A and failing it, then drug B and failing it, and then drug C using A, B and C, all together

Another evolutionary biologist working in this field is Heinrich Schulenburg, from the Christian-Albrechts University in Kiel, Germany.

"One idea that interests us especially is 'sequential therapy' "He says. That means giving different antibiotics a quick start ovality – say, change every 12 or 24 hours, so the embryonic environment is always changing. "

" From evolutionary theory, we know that it makes it very difficult for any organism to adapt quickly to their conditions, "he says.

Schulenburg tested this idea successfully in Petri and is now preparing to test the concept in humans.

"The question that we, as evolutionary biologists, want to make is that of any kind

a company called Synthetic Biologics in Rockville, Md., is developing an anti-inflammatory drug – an enzyme that actually destroys common antibiotics called beta lactams. such as penicillin. Their strategy is to give these pills to people who receive antibiotics injected directly into the bloodstream.

"Our enzyme stays in the intestine and is not absorbed in the blood, so it does not affect the efficacy of antibiotics," says Sheila Connolly, vice president of company research.

The enzyme destroys the antibiotics in the gut, which is where they most likely lead to drug resistance. Resistance characteristics can also be transmitted from one bacterial species to another, making the gut a boiler with an evolution of super-grace.

"If we can avoid exposing the gut to antibiotics, then we prevent the evolution and emergence of antibiotic resistance," Connelly develop a potentially lethal condition called C. difficile which is triggered when antibiotics kill too many "good" bacteria in the gut.

The company is currently planning extensive clinical trials to test the safety and efficacy of its product. (He is also working on a time-release version designed to be taken with oral antibiotics that would allow these drugs to be absorbed into the bloodstream before they are started.)

Connelly is optimistic about the economic outlook for this medicine. The enzyme can be cheaply produced, she says, and unlike new drugs that are often held in reserve, this one can be widely used by people who take ordinary antibiotics.

"I think there may be creative ways to buy us time," says Frank of the Biotechnology Trade Group. "I firmly believe that we will almost certainly never outgrow bacteria with our current arsenal. We will always develop new drugs. "

Schulenburg agrees that these methods will not be a cure for all the precarious role of antibiotics." I think the most important solution is to use less, "he says.

You can contact NPR Research correspondent Richard Harris on rharris @ npr.org .


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