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Debate Over Health Hazards of Putting Antibiotics
in Animal Feed Heats Up in the USA

CHEMICAL & ENGINEERING NEWS
October 25, 1999

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

The 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 exact figures are 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.

Antibiotic resistance by microorganisms that cause disease in humans and
animals has risen sharply over the past several decades, not only in the
U.S. but in much of the world. And evidence is accumulating that this
resistance is promoted by the antibiotics given to livestock.

CDC maintains that, based on the scientific evidence, steps are needed now,
not at some time in the future, to decrease the use of antibiotics in
livestock, especially as growth promoters. "It is clear that the increasing
resistance in some foodborne pathogens is the direct consequence of
antibiotic use in food animals," says Frederick J. Angulo of CDC's National
Center for Infectious Diseases.

However, according to a report from the General Accounting Office released
in April, the Department of Agriculture claims that more research is needed
before 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 the
issue, refused to talk to C&EN.

Last fall, the Food & Drug Administration proposed a framework for
evaluating the safety of antibiotics for use in livestock and their
capacity for promoting antibiotic-resistant bacteria in humans. But most
observers believe it would take decades to ban the use of an existing
antibiotic under this framework because it has no deadlines.

One reason CDC is concerned about antibiotic use in livestock is that
foodborne illness has become an increasing problem in the U.S. and causes
many more deaths than it did a decade ago. CDC estimates that 76 million
people 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 foodborneCampylobacter infections
results in the paralyzing disease Guillain-Barré syndrome. A strain of
Escherichia coli, E. coliO157: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 pressure 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 antibiotic-resistant 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., fluoroquinolone-resistant Campylobacter
have appeared in humans who have never been exposed to these drugs, he
says. This was unheard of prior to 1995, when fluoroquinolones began to be
used in the poultry 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 levels of vancomycin-resistant
enterococci in humans have declined in Europe, Angulo says.

Ever since the EU banned four human antibiotics as growth promoters in
livestock, the consequences have been carefully monitored. Already, the
levels of antibiotic-resistant bacteria in EU food animals have declined,
Angulo says.

Some U.S. public interest groups have been working hard to convince FDA to
phase out the use of human antibiotics as growth promoters in livestock. In
March, the Center for Science in the Public Interest, the Environmental
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
penicillin, 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, science cannot say that, if we reduce
antibiotic use in livestock by X, we will get Y fewer upset stomachs and Z
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 important
first step of taking antibiotics out of animal feed," she explains.

In contrast, a National Research Council report released in July held a
middle-of-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 promote such resistance. But not enough is known to
determine the extent of the public health risks posed by such transmission,
the report says. The report notes that phasing out antibiotics as growth
promoters in livestock in the U.S. would cost $4.85 to $9.72 per person
annually in higher meat and fish prices.

The NRC report also claims that antibiotic use in livestock generally
enhances 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 University,
Manhattan.

The Washington, D.C.-based Animal Health Institute, which represents
feed-additive manufacturers, maintains that there is little evidence
linking antibiotic use in agriculture to increased antibiotic resistance in
humans. It says in comments to FDA that the new framework document will
provide too many barriers to the approvals of new antibiotics for feed
additives. As long as experts both inside and outside the government have
such opposing views, the controversy over drug use in livestock will
probably remain unresolved.

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