Fight Resistance - Pharmaceutical Executive


Fight Resistance
Doomsayers predict that the post-antibiotic age is coming. But rising rates of antimicrobial resistance show that in many parts of the world, it is already here.

Pharmaceutical Executive

Admittedly, bacterial resistance presents a much different profile than traditional "neglected" diseases (take dengue fever, for example, which occurs primarily in parts of the world where there are no profits to be had from developing a new drug). And they're not true orphan drugs, because so many people are affected by resistant bacteria. However, given the importance of antibiotics to safeguard the well-being of the population, the provision was accepted.

Another promising piece of legislation is the Strategies to Address Antimicrobial Resistance, or STAAR, Act. Introduced in November 2007, STAAR delineates a multipronged approach to coordinate and fund federal activities related to antibiotic resistance, such as surveillance and control efforts—including monitoring antibiotics in food.

But the solution is not just more funding—it's smarter funding. In this regard, says Margaret Riley, NIAID traditionally has been too conservative about funding risky research. For instance, she says the current theory of the development of AMR needs fine-tuning. Riley points to a study that found bacteria like E. coli and Klebsiella have the same rates of resistance in the outback of Australia as in high-traffic clinical settings. What's more, patients in India, Turkey, and Poland had MRSA before they had methicillin.

"The problem with just coming up with the next gold standard is that all of that genetic variation that allows bacteria to fortuitously evade an antibiotic is already in their population somewhere," says Riley.

Riley's own research (funded, admittedly, by NIAID) looks at bacteriocins, which are highly targeted proteins produced by bacteria that can kill or inhibit other bacteria. Some people consider bacteriocins narrow-spectrum antibiotics—and because of that targeting, says Riley, resistant strains would take longer to evolve and spread.

Other scientific theories are also gaining steam, says Cubist's Eisenstein, who has sat on NIAID review committees. He ticks off a series of scientific ideas, including decreasing bacteria's mutation rates, altering quorum sensing—the process through which bacteria communicate with one another—or inhibiting bacterial efflux pumps, which are thought to play a role in AMR. But they are still a long way off from becoming a drug. "Quite frankly, none of them will turn into drugs in the next decade," says Eisenstein.

What Industry Can Do

Clearly, one is still left to wonder who will help the developing world when its antibiotics no longer work.

Certainly, this is an area where public/private partnerships can help. For example, the nonprofit Institute for One World Health worked with a range of entities to bring an injectable version of paromycin to India to cure visceral leishmaniasis—better known as "black fever." Other partnerships include the Alliance for the Prudent Use of Antibiotics, which focuses on antimicrobial stewardship, and the United States Pharmacopeia's Drug Quality and Information program, which focuses on counterfeiting.

Another way in for industry might be through vaccines. "A person might say, 'What are you talking about, vaccines? We're talking about resistance to drugs,'" says NIAID's Fauci. "Well, if you prevent infections, then you don't have to treat them. The less treatment, the less exposure to the selective pressure of antimicrobials that pushes microbes to resistance."

Wyeth's pneumococcal vaccine Prevanar, which prevents infections caused by S. pneumoniae, offers an example. Wyeth turned Prevanar into a blockbuster drug by proving its health value in developed markets, but also by talking to governments in the developing world about the overall economic productivity this vaccine can confer on a nation. "Demonstrating that the pneumococcal conjugate vaccine is successful stimulated competition," says Projan, "but it also stimulated other companies to think that, yes, you can not only do good for society but also do well commercially with an effective and safe vaccine."

But back in a village in Uganda, Jacky Tumusiime doesn't count Prevanar among the emergency supplies she carries to tend to the sick. Instead, she talks about counterfeit antibiotics from India, about wishing Augmentin and other drugs were available, about giving children drugs that just don't work. To the developed world, this may sound like merely a story of unfortunate circumstances happening to somebody else. But what's important to remember is that bacteria know no boundaries, no borders. And while researchers worry about the pathogens developing on their turf, in this era of rapid travel and globalized commerce, it's important to remember that the developing world's problems—and its bacteria—are only a plane ride away.


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