A BUG'S LIFE

The Government's Role in Taming Antibiotic-Resistant Bacteria

Judging by the popularity of the movie Outbreak, and books like The Coming Plague and Virus Hunter, there is a public fascination with deadly new diseases. As the last title indicates, these accounts focus on emergent viral infections. Medical research has developed few tools to combat viruses; hence the fear of deadly strains.

The public seems less concerned about the threat of serious bacterial epidemics. Despite the availability of over one hundred antibiotics, growing resistance to this arsenal means that the next plague could well be bacterial rather than viral. Although the topic hits the newspapers a couple of times a year and Congress holds the occasional hearing, there is little evidence that the issue is on most politicians' or the people's radar screen.

This indifference is paradoxical and perverse, because we have a much greater ability to manage the risk of bacterial outbreaks -- and yet, we may be squandering that power. Here's the rub: we overuse antibiotics, and this accelerates the rate at which bacteria develop resistance. Officials at the Centers for Disease Control estimate that a third of all outpatient antibiotic prescriptions issued in the United States are unnecessary. The World Health Organization puts the figure at fifty percent worldwide. Although antibacterial soaps and cleansers might seem distinct from medicine, the fast-growing use of these products also helps spread resistant strains. And humans are not the only users. Farm animals consume almost half the antibiotics bought in America. Only ten percent of these are used to treat specific illnesses in animals. The rest is added to feed, in low doses, merely as a growth enhancer.

In response to this onslaught, bacteria react. By the process of natural selection, those with greater resistance survive and thrive in the presence of antibiotics. And resistance develops not only through random mutations. Bacteria, in a sense, are incredible sexual -- and not just with their own species. They constantly swap little snippets of DNA, which often contain genetic formulae for resisting antibiotics. Once one type of bacteria evolves resistance to a particular antibiotic, the newfound defensive technique spreads directly to other species via these genetic exchanges.

The results are deeply troubling, to put it mildly. In Southeast Asia, ninety-eight percent of all gonorrhea patients now exhibit a penicillin-resistant strain of the bacteria. And such resistance can spread with surprising speed. During the 1980s, the presence of resistant salmonella bacteria in farm animals increased from thirty-nine percent to ninety-seven percent.

For salmonella, gonorrhea and most other bacterial infections, doctors thwarted by resistance to one antibiotic can turn to another. During the 1980s, however, "superbugs" resistant to even the high-powered antibiotic of last resort, vancomycin, emerged. If harmful bacteria evolve full resistance to vancomycin, the Mayo Clinic has declared that we would have a "serious crisis" on our hands. The appearance of partially vancomycin-resistant staph infections in 1997 raised the specter of just such a crisis.

The picture is not entirely grim. True, there was a lull in the development of antibiotics during the 1970s and 1980s -- a time when bacteria seemed permanently whipped by the large array of antibiotics available. But worry about resistant strains has reinvigorated research. Over the last two years, academic and industry scientists have discovered at least three new antibiotics capable of eradicating vancomycin-resistant bacteria.

The most obvious problem is that individuals have little incentive to limit their use of antibiotics to cases of real need. Like thousands of American parents every day, I have pressured my daughter's pediatrician to prescribe antibiotics for inner ear infections despite the high likelihood that the culprit is viral. In addition, even if the problem is bacterial, it may not be in our long-term interests to rely on antibiotics to kill mild infections. Overuse of an antibiotic to treat today's mild ear infections might well mean total inability to treat life-threatening infections ten years from now.

This is what academics call a "tragedy of the commons" problem -- at root, little different from the problem of littering in public parks. What is individually rational (using an antibiotic for mild infections; neglecting to put personal trash in receptacles) is bad for the community as a whole in both cases.

Serendipitously, the monopoly over drug sales granted by the patent system helps to alleviate this problem. Higher prices discourage use. This preserves the potency of antibiotics for more serious cases. Yet even monopolists (whose incentives to raise prices are limited by demand for a product) may not charge a high enough price to prevent some unnecessary use (at what price would you forgo an antibiotic for your daughter's ear infection?). The government may need to impose a tax on antibiotics, or command that doctors prescribe the more valuable antibiotics only for a defined set of serious conditions. In Canada and Denmark, strict regulations limiting the use of key antibiotics to cases of true necessity have significantly reduced the occurrence of resistant bacteria.

The federal government and the states may want to follow suit in some situations -- for example, barring the use of the new antibiotics that work where vancomycin fails, except in the most dire of cases. Such high-powered medication is like the army. It is very important to have, but in the best of all worlds a nation never uses it. The prospect of such draconian regulation, however, undoubtedly sends shudders down the spines of pharmaceutical executives. We cannot expect drug makers to develop products that they can sell only in small quantities, if at all. So to the extent that key antibiotics are like the army, they are public goods that the state alone can provide. The government must fund the research necessary to discover antibiotics of last resort.

Another problem is the length of patent law's monopoly -- twenty years. If the government regulates use for extended periods of time, the twenty-year period should be tolled to preserve incentives to discover new antibiotics. In addition, we may need private actors to take a longer perspective. If the odds of a bacterial plague occurring within twenty years are low, but within fifty or one hundred years are high, the patent system offers far too little carrot to encourage pharmaceutical makers to find new antibacterial agents. In order to encourage research and development of antibiotics that may not become useful within twenty years, Congress should consider granting longer patent monopolies.

The most daunting aspect of the problem is that it is global. Given the mobility of man and microbes, a problem in Zanzibar can become a problem in Alabama before it is detected. Trying to curb overuse of antibiotics requires regulation in every single nation; any plan will be only as strong as its weakest link. Just as it is rational for the United States to spend millions of dollars tracking, treating and researching the Ebola virus when it affects only a few Africans halfway around the globe, so too our tax dollars are well spent helping poorer nations rationalize their use of antibiotics. The number of arrows in our antibacterial quiver is dangerously low.