g o v e r n m e n t & policy
Livestock Antibiotic Debate Heats Up FDA, CDC, USDA, public interest groups dispute extent to which human illnesses are linked to animal antibiotic use Bette Hileman C&EN Washington
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fore decisions are made regarding further restriction on antibiotic use in food animals. USDA argues that subtherapeutic levels of antibiotics added to animal feed— less than 200 g per ton—prevent low-level infections, allow animals to use feed more efficiently, and prevent serious disease outbreaks. USDA experts, citing the controversy surrounding
he use of antibiotics in livestock to reduce disease and promote growth has been controversial for many years. But the debate has heated up as concern grows that bacteria that cause illnesses in humans are becoming more resistant to antibiotic medicines because of overuse of the same antibiotics in livestock. Federal agencies and other organizations are grappling for solutions to the problem, but the trouble is that they are coming down on opposite sides of the fence. No exactfiguresare available, but the Centers for Disease Control & Prevention (CDC), Atlanta, estimates that 50 million lb of antibiotics is produced each year in the U.S. and about 40% of that is used in livestock, mostly for growth promotion. Nearly 80% of farm animals—mainly cattle, pigs, and poultry—receive subtherapeutic levels of antibiotics in their feed, at least part of the time. Clockwise from above: Antibiotic resistance by miHalloran, Reed Herbert, croorganisms that cause disease and Angulo in humans and animals has risen sharply over the past several decades, the issue, refused not only in the U.S. but in much of the to talk to C&EN. world. And evidence is accumulating Last fall, the that this resistance is promoted by the Food & Drug Adantibiotics given to livestock. ministration proCDC maintains that, based on the sci- posed a framework for evaluating the entific evidence, steps are needed now, safety of antibiotics for use in livestock not at some time in the future, to de- and their capacity for promoting antibicrease the use of antibiotics in livestock, otic-resistant bacteria in humans. But especially as growth promoters. "It is most observers believe it would take declear that the increasing resistance in cades to ban the use of an existing antisome foodborne pathogens is the direct biotic under this framework because it consequence of antibiotic use in food ani- has no deadlines. mals," says Frederick J. Angulo of CDC's One reason CDC is concerned about National Center for Infectious Diseases. antibiotic use in livestock is that foodHowever, according to a report from borne illness has become an increasing the General Accounting Office released in problem in the U.S. and causes many April, the Department of Agriculture more deaths than it did a decade ago. claims that more research is needed be- CDC estimates that 76 million people 32
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become ill each year and 5,000 die from food contaminated with viruses, bacteria, parasites, toxins, or metals. Each year, CDC says, an estimated 8,000 to 18,000 hospitalizations, 2,400 bloodstream infections, and 500 deaths are associated with foodborne Salmonella infections. One in 1,000 foodborne Campylobacter infections results in the paralyzing disease Guillain-Barré syndrome. A strain of Escherichia coli, E. colt 0157:H7, has emerged that kills 50 to 100 people each year. In many cases, patients who become gravely ill or die are infected with bacteria—especially Salmonella, Campylobacter, and E. coli—that are resistant to all, or nearly all, antibiotics. However, it is not known exactly what proportion of these illnesses can be attributed to antibiotic resistance. At the same time that the incidence of foodborne illness has risen, FDA has found that the meat supply has become highly contaminated with bacteria. FDA's Center for Veterinary Medicine reports that 1% of beef, 8.7% of swine, and 20% of poultry carcasses are infected with Salmonella. Campylobacter is even more prevalent. It infects 4% of beef, 31.5% of swine, and 88% of broiler chicken carcasses. Also, data obtained by FDA's antimicrobial resistance monitoring system show that the levels of certain resistant bacteria in meat and poultry carcasses have increased over the past three years. Bacteria in meat and poultry are usually killed if the meat is cooked thoroughly. But people become infected from eating inadequately cooked meat or raw food that comes into contact with contaminated knives or cutting boards. "People do not treat their kitchens like high-risk biohazard research facilities," says Jean Halloran, director of the Consumer Policy Institute, the research arm of Consumers Union. CDC spokesmen say that one reason foodborne bacteria have become so highly resistant to antibiotics is that many of the same drugs used to treat humans are also given to livestock. "Nineteen classes of antibiotics are approved for use as growth promoters in animals. Of these, six are important, if not critical, antibiotics in human medicine," Angulo says. The antibiotics added to animal feed exert a selective pres-
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g o v e r n m e n t & policy sure on the bacteria in the animal's gut, killing those that are susceptible and sparing the resistant ones, he explains. Some of the resistant microbes then end up in food in the grocery store. Bacteria readily take up resistance genes from bacterial cells of different species. So it is inevitable that antibioticresistant bacteria in farm animals will spread their resistance to human bacteria, Angulo says. Another major, and probably more important, explanation of antibiotic resistance—which no one disputes—is the overuse of antibiotics in human medicine, especially for treatment of viruses. Forty percent of children who go to the doctor with a cold are given antibiotics, says Martha Reed Herbert, a pediatric neurologist at Massachusetts General Hospital. Most of these children are infected with viruses, which can't be killed with antibiotics. FDA's framework document sets out a conceptual, risk-based process for evaluating the human safety of antibiotic use in animals. It aims to ensure that antibiotics valuable for human health
are not lost because of their use in animals. Under the framework, if bacterial resistance to a particular drug reaches a certain threshold, actions to restrict its animal use would begin, including, as a last resort, withdrawal of approval of the drug for livestock use. Some observers say the document is primarily intended for evaluating new antibiotics because it includes a footnote saying FDA will assess existing drugs as resources allow. However, Sharon R. Thompson, associate director of veterinary, medical, and international affairs in FDA's Center for Veterinary Medicine, says the framework document is intended for the assessment of both new and existing antibiotics. The document is still being revised in response to the many comments received, she says. CDC's Angulo considers the framework document "an important step forward." However, he is concerned that the lack of specific goals or time frames will mean that it will take "many years before new regulations are in place under this framework and decades to assess the antibiotics that are already approved."
The European Union, the World Health Organization, and the American Public Health Association hold positions similar to CDC's. They all favor the immediate phaseout of antibiotic growth promoters that are the same as, or closely related to, antibiotics used in humans. The U.K. banned the use of penicillin and tetracycline for livestock growth promotion in the early 1970s, and other European countries took the same step shortly after. In the mid-1970s, FDA proposed a similar ban, but Congress intervened and required FDA to do more research before instituting a ban. Sweden banned the use of all antibiotics for growth promotion in 1986. Last December, the EU banned four antibiotics as growth promoters that are used, or related to those used, in human medicine. New evidence—much of it reported at the spring meeting of the American Society for Microbiology held in Chicago—provides a strong link between antibiotic use in livestock and antibiotic resistance in human disease bacteria, Angulo says. In the U.S., fluoroquinoloneresistant Campylobacter have appeared
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in humans who have never been ex posed to these drugs, he says. This was unheard of prior to 1995, when fluoro quinolones began to be used in the poul try industry, and resistant bacteria is a result of such use, he says. In 1997, the analog of the antibiotic vancomycin was withdrawn as a growth promoter in the EU. As a result, the lev els of vancomycin-resistant enterococci in humans have declined in Europe, Angulo says. Ever since the EU banned four human antibiotics as growth promoters in live stock, the consequences have been care fully monitored. Already, the levels of an tibiotic-resistant bacteria in EU food ani mals have declined, Angulo says. Some U.S. public interest groups have been working hard to convince FDA to phase out the use of human anti biotics as growth promoters in live stock. In March, the Center for Science in the Public Interest, the Environmen tal Defense Fund (EDF), and several other groups petitioned FDA to rescind approvals for subtherapeutic uses in livestock of six antibiotics that are used
in or related to those used in human medicine. The ban should include peni cillin, tetracycline, erythromycin, lincomycin, tylosin, and virginiamycin, the petition says. "It's about time that FDA stopped protecting the profit margins of agribusiness and started protecting public health," says Rebecca J. Goldburg, senior scientist at EDF. Halloran agrees. "At this time, sci ence cannot say that, if we reduce antibi otic use in livestock by X, we will get Y fewer upset stomachs and Ζ fewer deaths," she says. "Even though you can't establish that sort of relationship, you should make a leap of faith and take a very importantfirststep of taking anti biotics out of animal feed," she explains. In contrast, a National Research Coun cil report released in July held a middleof-the-road position. It concludes that bacteria that resist antibiotics can be passed from food animals to people and that antibiotic use in livestock can pro mote such resistance. But not enough is known to determine the extent of the public health risks posed by such trans mission, the report says. The report
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notes that phasing out antibiotics as growth promoters in livestock in the U.S. would cost $4.85 to $9.72 per person an nually in higher meat andfishprices. The NRC report also claims that anti biotic use in livestock generally enhanc es the health of the food supply. "Using antibiotics to control and treat diseases in animals improves the safety of our food supply by providing healthier sources of meat, cheese, milk, and eggs," said committee chairman James R. Coffman, provost at Kansas State Uni versity, Manhattan. The Washington, D.C.-based Animal Health Institute, which represents feedadditive manufacturers, maintains that there is little evidence linking antibiotic use in agriculture to increased antibiotic resistance in humans. It says in com ments to FDA that the new framework document will provide too many barri ers to the approvals of new antibiotics for feed additives. As long as experts both inside and outside the government have such opposing views, the contro versy over drug use in livestock will probably remain unresolved.^
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