The Rise of Antibiotic Resistance: Consequences of FDA's Inaction

By allowing big food to self-regulate when it comes to using antibiotics as a growth promoter in animals, the FDA is setting us up for disaster.

Two weeks ago, the Food and Drug Administration (FDA) announced that it would ban certain off-label uses of cephalosporin antibiotics in animal agriculture, asserting that these uses posed an undue risk of selecting for antibiotic-resistant bacteria. Many of us who follow this issue closely recognized FDA's move for what it was: a distraction from the fundamental need for change. The cephalosporin announcement came just two weeks after FDA refused to restrict the use of two other important antibiotics in food animals. It looked to be a thinly veiled effort to deflect criticism of this refusal.

With the occasional exception, like cephalosporins, FDA has failed for decades to take meaningful action on the misuse of antibiotics in food animal production -- misuse that directly contributes to the selection of antibiotic-resistant bacteria and compromises our ability to treat bacterial infections.

THE NEXT EPIDEMIOLOGIC TRANSITION

In 1900, the three leading causes of death in the United States were pneumonia, tuberculosis, and enteritis -- all infectious diseases. A century later, heart disease, cancer, and stroke -- all chronic, non-infectious diseases -- had replaced these at the top of the list. The shift in leading causes of death from infectious to chronic diseases is partly credited with raising average life expectancy by over 30 years. Much of this increase has been attributed to massive reductions in infectious disease mortality, which disproportionately impacts the young. These shifts have come to be known as an "epidemiologic transition," perhaps the most notable achievement in the modern history of public health.

By the 1980s, however, common bacterial pathogens, including certain strains of Staphylococcus aureus, were increasingly found to be resistant to antibiotics. A particularly pernicious strain, methicillin-resistant Staphylococcus aureus, has become a widely recognized cause of serious disease and death. Well-known pathogens like Streptococcus pneumoniae (the causative agent of many pneumonias) and Salmonella are more frequently found to be resistant, and difficult-to-treat infections with these pathogens are becoming more common. Dr. Margaret Chan, director-general of the World Health Organization (WHO), did not mince words when she warned last year, "the world is heading toward a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated."

Epidemiologists now contend that we have entered the next transition -- one marked by, among other things, the increasing resistance of bacteria to antibiotics.

UNDERSTANDING RESISTANCE

When a physician prescribes an antibiotic to treat an infection, he or she will select the specific antibiotic and dose that are most likely to cure the disease. If the wrong antibiotic is chosen or the dose is too low to treat the disease, some bacteria -- those most resistant to the drug used -- will survive and reproduce, allowing the disease to return or prolonging the resolution of the infection.

Most of the food animals fed antibiotics are not diseased. Nor would the amounts they receive be high enough to treat disease if they were. Rather, food animals are continuously fed small quantities of antibiotics throughout their lives to make them grow faster. Today, the overwhelming majority of antibiotics in this country -- nearly 80 percent -- are sold for use in food animals, not humans.

The development of resistance is Darwinian evolution on a microscopic scale. Bacteria compete with each other for limited resources. Some bacteria are more susceptible to antibiotics than others, and become less able to compete when exposed to an antibiotic. Repeated exposure to an antibiotic will continue to make resistant bacteria better competitors, allowing them to increase their numbers relative to the susceptible organisms -- especially when continuously exposed to the low doses of antibiotics typically used in industrial food animal production. This practice facilitates and promotes the development of antibiotic resistance -- and threatens public health.

Resistant bacteria have been shown to remain in the animal as it is raised and slaughtered, and to persist on the animals' meat following slaughter. Exposure to these bacteria can lead to infections that do not respond to treatment, as evidenced by recent outbreaks of foodborne illness. Hannaford grocery stores recently recalled ground beef after 19 people in seven states who ate the beef were sickened by resistant Salmonella Typhimurium. Late last year, Cargill Meat Solutions recalled more than 36 million pounds of ground turkey after 136 people in 34 states fell ill with resistant Salmonella Heidelberg.

Food is not the only means by which resistant bacteria from farms can infect humans. Workers at industrial food animal production and processing facilities have regular contact with animals and can contract resistant infections from them. They can also carry resistant bacteria on their clothing and can transmit them to family and friends. Additionally, the ventilation of animal production facilities and food animal transport trucks can release resistant pathogens to the air, exposing those on farms and others nearby who breathe this air. Animal manure also contains resistant bacteria, and manure applied to crops as fertilizer can be washed into streams when it rains. These streams can carry the bacteria to bodies of water in which people swim and fish, exposing humans in more ways still.

A DEAFENING SILENCE

Unfortunately, the agency responsible for ensuring that animal drugs are used in ways that are effective for animals and safe for humans has been derelict in its duties for decades. Cephalosporins, the subject of the recent FDA announcement, are a group of antibiotics considered "critically important to human medicine" by the WHO. They are the treatment of choice for serious cases of salmonellosis (disease caused by Salmonella infection) that occur in children. They are also administered to poultry and dairy cattle in ways that have not been approved by FDA and, like the use of antibiotics for growth promotion, carry a high risk of selecting for cephalosporin-resistant bacteria. The ban announced by FDA would prohibit these uses and others. This is welcome news.

FDA's announcement on cephalosporins, however, comes after decades of inaction on the misuse of antibiotics in food animal production. Over the holidays, when few were watching, the agency gave notice that it would not restrict the use of penicillins or tetracyclines -- two groups of antibiotics likewise considered "critically important" by the WHO. FDA had considered restricting their use since 1977, but encountered strong industry pushback and elected not to take action. In 1999 and 2005, consumer advocacy groups petitioned FDA to follow through on its proposal and restrict use of both drugs. The agency ignored the petitions until last year, when it denied both.

With the exception of the ban on some uses of cephalosporin, FDA has decided to forgo further regulation of antibiotic use in animal agriculture. Instead, it has announced it will allow industry to make voluntary changes in the ways antibiotics are sold and used, despite no evidence that industry has any desire to change. Spokespeople for key industry groups continue to argue that antibiotics are used responsibly in food animal production. They deny that current use leads to resistant infections in humans, most recently in their responses to the proposed cephalosporin ban.

If the development of antibiotics was an important legacy of the last epidemiologic transition, the rise of antibiotic resistance is a harbinger of the next one. We know that infectious diseases will always be with us, and that they will evolve in ways that are often beyond our direct control.

The rapid rise of resistance is not one of these ways. It has resulted directly from the misuse of antibiotics, especially in animal agriculture. To slow the evolution of resistance and preserve the efficacy of antibiotics for current and future generations, we must ensure their responsible use. FDA must act.

Image: Nenov Brothers Photography/Shutterstock.