CHAPTER

20

Getting Serious About Antibiotic Resistance

by Ramanan Laxminarayan

Every year in America, some 40,000 people die from infections caused by antibiotic resistant bacteria, only slightly less than the number of those killed on our roads. This may actually be an underestimate, because many other deaths, particularly those of elderly patients suffering from a myriad of problems, may in reality be caused by these so-called superbugs. Mr. President, in order to address this serious threat to the nation’s public health, I recommend that you introduce legislation to discourage the use of antibiotics where they bring little benefit to patients. These measures would include increasing cost-sharing for antibiotics under Medicare and Medicaid, while expanding coverage and subsidies for cough and cold medications that patients may use instead of antibiotics. In addition, a large proportion of antibiotic use in the United States is by the animal industry to help farm animals gain weight faster. Studies indicate that the benefit of using antibiotics for this purpose is greatly outweighed by the cost imposed on the rest of society in terms of reduced antibiotic effectiveness. In light of this, I also propose a ban on the use in growth promotion of all antibiotics that are currently being used to treat human infections.

The Problem

Modern medicine rests on the bedrock of the availability of affordable and effective antibiotics. In recent years, bacteria have been increasingly resistant to antibiotics, threatening our ability to treat previously treatable illnesses. Reports of methicillinresistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae are increasingly common, to name just two dangerous pathogens. In fact, the prevalence of high-level penicillin resistance in S. pneumoniae in the United States grew 800-fold between 1987 and 1999, from 0.02 to 16.5 percent. According to the U.S. Food and Drug Administration (FDA), “Unless antibiotic resistance problems are detected as they emerge, and actions are taken to contain them, the world could be faced with previously treatable diseases that have again become untreatable, as in the days before antibiotics were developed.” While the nation’s focus has remained steadily on bioterrorist threats, a potentially greater threat already is lurking in our hospitals and communities and requires immediate attention.

Antibiotics have been in use in medicine since the 1940s and are now widely used for a variety of reasons, ranging from ear infections in children to keeping patients undergoing transplants free of infection. Although resistance has been increasing for a number of reasons, the underlying driving force is largely that doctors and patients who overuse, and sometimes misuse, antibiotics have no incentive to take into consideration the impact of their actions on the rest of society. This results in the use of antibiotics to treat viral and other conditions where they have no effect (antibiotics cure bacterial infections only), inadequate compliance by patients with treatment regimens, poor dosing by doctors, and lack of infection control, all of which have led to decreasing drug effectiveness.

And antibiotics are not only used in treating humans, but they also are used in livestock to help them gain weight faster (subtherapeutic use) and to avoid and treat disease (prophylactic and therapeutic use). It is estimated that more than half the antibiotics produced in the United States are used in the animal health industry, and the bulk of this is for growth promotion. Because these uses promote the development of drug-resistant bacteria in animals, and routes exist for the movement of these resistant bacteria to humans, drug resistance in bacteria associated with food animals can influence the level of resistance in bacteria that cause human diseases. Several compelling studies have documented the impact of subtherapeutic use of antibiotics on resistance in humans, and the evidence is mounting. Population biology predicts that the strong selection pressure imposed by the use of antibiotics in animal feed will lead to the evolution of resistant microorganisms. Although more studies will help improve our understanding of the links between antibiotic use in animals and resistant infections in humans, our wait for even more conclusive evidence will come at the cost of losing valuable drugs that will be very expensive to replace.

Recommendations

I recommend that you consider making two policy changes. The first is to discourage inappropriate antibiotic use with a combination of price and nonprice measures. Price measures would include subsidies or expanding Medicaid and Medicare coverage for over-the-counter substitutes for antibiotics, such as cough medicines and pain relievers. They also would increase copayments for antibiotics prescribed for conditions for which their use would bring little benefit to patients but would harm society by increasing drug selection pressure. Such price measures need to be combined with nonprice measures that include patient and physician education, better resistance surveillance data, increasing antibiotic heterogeneity, and providing warning labels on antibiotics. These nonprice measures alone are likely to be ineffective without a compelling economic incentive for patients and physicians. They must shoulder the cost that they impose on the rest of society in the form of resistance when they overuse or misuse antibiotics.

Second, I propose that you ban the use for animal growth promotion of antibiotics that are used in treating humans, unless the pharmaceutical companies can demonstrate that their use in growth promotion has no demonstrable impact on the evolution of resistant pathogens.

Raising the Costs of Antibiotics

The most reliable axiom in economics is that as the price of any commodity goes up, the quantity of that commodity that people will consume declines, all else being equal. Therefore, the most reliable way of reducing the use of antibiotics without second-guessing physicians’ decisionmaking is by raising their costs to patients.

One solution might be to impose a tax on antibiotics, but this may be undesirable for two reasons. First, a tax may not discourage antibiotic use if insurance coverage shields many patients from drug costs and physicians are relatively insensitive to drug costs. Second, the burden of a tax may be borne disproportionately by poorer patients, who are less likely to have health insurance to cover the cost of antibiotic prescriptions.

A logical alternative would be to mandate an increase in the extent of cost-sharing for antibiotics. This could be accomplished by increasing copayments for antibiotic prescriptions for certain conditions for which a regulatory or scientific body believes that antibiotics are overprescribed, such as for the treatment of ear infections. Such a measure would not hurt the majority of economically disadvantaged patients who lack prescription drug coverage, but it still would effectively tax antibiotic use.

To be sure, a price-based policy intervention is a blunt instrument, and it may, in some instances, discourage the use of antibiotics even when their use is justified. However, targeted cost-sharing efforts aimed at certain diagnoses may be preferable to an across-the-board increase in mandatory cost-sharing for all antibiotics. Increased cost-sharing or other methods of raising the costs of antibiotics to patients may not be popular. But short of direct case-by-case oversight of prescriptions, few other alternative strategies could effectively lower antibiotic use.

Banning Use in Growth Promotion

Under a measure banning the use of antibiotics for growth promotion in animals, their use to treat sick animals would still be permitted. Although this policy change may raise the cost of meat production in the short term, and perhaps even increase the volume of antibiotics used to treat sick animals in the long term, withdrawing antibiotics as an input in the animal industry can bring great benefits to public health and safety.

Some countries in Europe already have adopted such a ban, and the lessons from their experiences can help guide your administration’s decisionmaking. In Denmark, a ban on antibiotic use in swine production significantly lowered the use of antibiotics in growth promotion and raised the cost of swine production by less than 1 percent. Although it appears that the ban may have resulted in a higher incidence of disease among swine and a greater use of antibiotics used to treat sick animals, this may be just a short-term effect. The Danish farms that had the greatest difficulty coping with the withdrawal of antibiotics were those that were older and had poorer hygiene and less sanitary conditions. The use of antibiotics should not be a substitute for more modern methods of hygiene. A similar increase was noted in Sweden, where antibiotic use in animals was banned in 1986, but there this was a temporary problem. Over the longer term, livestock producers were able to move to an effective production system with lower antibiotic use.

International consensus is growing on the need to safeguard our arsenal of antibiotics. The World Health Organization recommends that antimicrobials normally prescribed for humans should no longer be used to promote growth in animals. The European Union plans to phase out such use before 2006. The FDA already has recommended a withdrawal of the use of one class of antibiotics, fluoroquinolones, for use as growth promoters. These powerful antibiotics, which include the drug Ciprofloxacin, are valuable in treating people.

Conclusions

The problem of antibiotic resistance is of great concern to many federal agencies, although no single agency has a mandate to safeguard the effectiveness of these drugs. An interagency task force currently is looking into educational measures targeted at physicians and patients to reduce antibiotic prescribing, among other alternatives, to address the problem of drug resistance. However, without specific measures to create incentives for physicians, patients, and managed-care organizations to change their practices, these educational measures will not go far enough in curbing inappropriate antibiotic use.

For all of these reasons, I recommend that you support the bill introduced by Senators Edward M. Kennedy and Jack Reed, Preservation of Antibiotics for Human Treatment Act of 2002. Additionally, I propose that you expand this bill to include not just the use of antibiotics in animals, but also measures that address the use of antibiotics in humans. Finally, I urge you to act expediently. Our history of using antibiotics is only 60 years old, and we already are in danger of relying on using our most powerful drugs to treat humans. Increasing resistance may be irreversible, but managing these drugs as valuable societal resources may extend their usefulness to future generations.

One last consideration is that antibiotics are among our most valuable assets in defending against bioterrorism. Stockpiling antibiotics in case of an emergency does no good if these antibiotics are rendered ineffective by improper use. Without a farsighted, comprehensive agenda for dealing with drug resistance and coming up with imaginative solutions to a problem that is growing steadily worse, our ability to control infectious diseases is in danger.

R.L.