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How to Stop the Rise of Superbugs

Monday, June 3, 2013

The rise of 'superbugs' is causing tens of thousands of deaths a year in the United States alone. A problem as complex as antibiotic resistance will require several solutions.

Increasing antibiotic resistance is of great concern — the health of millions is dependent on our ability to defeat the threat of infectious diseases. The World Health Organization estimates that multi-drug resistance accounts for more than 150,000 deaths each year from tuberculosis alone.

Without effective antibiotics in health care, humanity would be thrown back to the time when urinary tract infections and pneumonia were lethal. Infant and maternal mortality would rise and ordinary surgical procedures would become risky to perform.

Methicillin-resistant Staphylococcus aureus (MRSA) is the most frequently identified drug-resistant pathogen in U.S. hospitals. Outbreaks of community-associated MRSA infections have been reported in correctional facilities, the National Football League, military recruits, and newborn nurseries. MRSA infections now appear to be endemic in many urban regions, spreading in limited geographical areas, but there is a risk of an epidemic outbreak.

Since the first reports of healthy, young children dying of severe MRSA infections in 1999, the number of deaths from MRSA infection in the United States each year has risen to tens of thousands — outstripping those caused by AIDS.

In March, the Centers for Disease Control sounded the alarm on the spread of carbapenem-resistant Enterobacteriaceae, or CRE. So far, the rare bacteria has been found only in hospitals or nursing homes. In 2001, only 1.2 percent of the common family of bacteria Enterobacteriaceae were resistant to carbapenem antibiotics — the strongest class available. By 2011, that figure had jumped to 4.2 per cent.

Possible Cures

The debate over antibiotic resistance often pits individual choice against public health. Patients are said to demand too many antibiotics from their doctors. Both the Food and Drug Administration and the CDC advocate reducing the use of antibiotics in order to prevent resistant bacteria. Demand-side policy is trying to slow down bacteria’s strength — a rapid evolutionary process — and is not necessarily the best solution.

The relationship between prescribed antibiotics and the spread of resistance is not clear. In Sweden, which has one of the lowest intakes of antibiotics in the world, prescriptions declined by about 30 percent between 1992 and 2011. Yet the number of outbreaks of antibiotic-resistant bacteria have increased. The connection between antibiotic intake and the development of resistance is more complex than a mere link between consumption and resistance.

Outbreaks of community-associated MRSA infections have been reported in correctional facilities, the National Football League, military recruits, and newborn nurseries.

The use of antibiotics as to promote growth in animals may also cause antibiotic resistance. The addition of antibiotics to animal feed was banned in the European Union, against the advice of its own Scientific Committee for Animal Nutrition. Despite a decrease in antibiotic use, resistance has not decreased correspondingly. The use of antibiotics in agriculture probably does not play as important a role in the development of resistance as does the increased use of antibiotics for humans and pets.

Another possible factor contributing to antibiotic resistance is doctors’ difficulty in properly distinguishing between a virus and bacteria when diagnosing a patient, a problem that could be solved with better diagnostic tools for early detection. But if more knowledge is to create better medical practice, it is even more important to protect doctors' freedom to prescribe.

Unsanitary hospital environments and the negligence of cleaning staffs have also been identified as contributors to antibiotic resistance. Implementing new procedures for doctors and nurses would create more sanitary conditions.

The History and Science of Antibiotics

Antibiotics are one of medicine's greatest triumphs. Throughout history, epidemics of infectious diseases were a fact of life. In the 19th century, infections caused more than 20 percent of all deaths. Medical science saw modest success in the struggle against bacteria by improving hygiene in hospitals, using disinfectants, and promoting better diets, but the discovery of antibiotics dramatically improved medicine's success — it is hard to imagine modern medicine without antibiotics. Penicillin saved millions of lives and increased life spans all over the world. Tuberculosis could be medicated, pneumonia was no longer fatal, and syphilis, gonorrhea, meningitis, ear and urinary tract infections, and simple wound infections could be cured. Before antibiotics, infant mortality was 30 times higher than today.

Biologist Alexander Fleming discovered antibiotics almost by coincidence. He left his lab during a vacation in 1928 and a few spores of mold got into a culture of Staphylococci he was studying. The mold grew and killed the bacteria. Fleming quickly realized the potential of his discovery, but it took him a long time to develop it into a functional medicine. In the 1940s, he received the vital assistance of Howard Florey and Ernst Chain to develop penicillin. In 1945, the trio was awarded the Nobel Prize in Medicine.

In his Nobel Prize acceptance speech, Fleming identified the risk of bacteria becoming resistant to antibiotics. Bacteria that survive in an environment where antibiotics are plentiful will be able to pass on their resistance to other bacteria through natural selection or by plasmid exchange. If a bacterium carries several resistance genes, it is called multiresistant or, informally, a "superbug."

Scientists are not yet certain how antibiotics work on the molecular level, but think that they introduce reactive oxygen to bacterial cells and damage their structure. Development of other new antibiotics started soon after penicillin, with ampicillin, cephalosporins, erythromycin, carbenicillin, methicillin, streptomycin, and tetracycline. But in the last 20 years, only two new antibiotics have been developed, and thus bacteria are becoming more resilient.

Market Failures

Antibiotic-resistant bacteria are often framed as a "tragedy of the commons," with the depletion of a shared resource by individuals acting independently and rationally according to each one's self-interest. Thus, innovation and supply-side solutions are key.

Without effective antibiotics in health care, humanity would be thrown back to the time when urinary tract infections and pneumonia were lethal.

As John E. Calfee has noted, the pharmaceutical industry is indispensable, because success in drug development is seldom achieved without persistent risk-taking.

Few pharmaceutical companies still actively pursue the research for new antibiotics since the drugs are expensive to develop but are used only briefly by most patients. If new antibiotics are developed, they are supposed by be used only in extreme cases, so as to prevent bacteria developing resistance to them. Thus, companies do not have much incentive to develop new antibiotics. Antibiotics are said to provide an example of a market failure, and some say the government should therefore promote related research and even get into the production of antibiotics. The European Union currently funds the research of the pharmaceutical industry in a public-private partnership.

But government can also get in the way. The extensive testing of new antibiotics by the FDA inhibits innovation. Only one in ten compounds tested becomes a drug, a figure that is far too low given the costs of research. Today, it takes eight years before a drug is approved.

Of the antibiotics available in the market today, 75 percent were developed before 1970.

Rather than new antibiotics, research will probably discover a completely new type of solution to infections. The genes encoding antibiotic resistance in bacterial DNA are being studied in order to be reversed. IBM is exploring how nanotechnology can kill bacteria.

The Generating Antibiotic Incentives Now (GAIN) Act signed by President Obama last year provides incentives for innovation, adding five years of patent-exclusivity to qualified products used to fight infectious diseases. Such qualifying drugs also get "fast-track" approval by federal agencies. Combined with tax credits for research and development, the law provides incentives without further diminishing the degree of competition in the pharmaceutical market as a private-public partnership would.

It’s too early to see major results, and while the GAIN Act offers a promising approach to finding solutions, more needs to be done. The key constraint to overall improvement is the rigidity and regulation of the pharmaceutical market, which curtails consumer choice and limits innovation. Focusing on the approval process would be beneficial: today's process puts emphasis on uniformity, predictability, and security, but, to beat antibiotic resistance, medicine needs individualization, adaptability, and resilience. Introducing competition between certifying drug approval organizations, dual track approval processes, and promoting the use of biologics and nanomedicine would also be helpful. In addition, better diagnostics and information sharing would improve patient and doctor communication regarding proper antibiotics treatment.

Antibiotic resistance is a race between humanity and bacteria. The bacteria's advantage is rapid adaptation to their environment; ours is ingenuity. There is no single solution to such a complex problem as antibiotic resistance. That is why we need to leave the field open for several solutions.

Waldemar Ingdahl is the author of a report on antibiotic resistance policy published by the Swedish think tank Timbro. He covers science and technology and has written several books in Swedish on health care policy.

FURTHER READING: Scott Gottlieb contributes “Attack of the Superbugs,” David Shayvitz argues “Drug Research Needs Serendipity,” and Roger Bate writes “Tuberculosis: Poor-Quality Medicines Contribute to Drug Resistance.” John E. Calfee discusses “The Indispensable Industry” and asks, “What Do Vitamins and Fish Oil Tell Us About Drug Research?

Image by Dianna Ingram / Bergman Group

 

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