Antibiotics in Animal Feed--A Growing Public Health Hazard
Worries Rise Over Effect of Antibiotics in Animal Feed

By Marc Kaufman
Washington Post Staff Writer
Friday , March 17, 2000 ; A01

A 66-year-old woman was recovering from a heart bypass in a hospital near
Detroit when she suddenly developed respiratory failure and a serious
infection. Doctors quickly gave her an antibiotic that usually works. This
time, however, it didn't. The bacteria causing the woman's infection were
resistant to the drug.

The woman's doctors immediately turned to a newly approved antibiotic, a
powerful one designed specifically to attack the kind of dangerous
antibiotic-resistant microbes that had infected her. But her physicians
were dismayed to find that drug didn't work either--the bacteria in her
body were resistant to it as well. The woman died soon after.

Cases like this around the country have caused rising alarm among
infectious disease doctors and public health experts. They are also at the
center of an increasingly acrimonious dispute now before the Food and Drug
Administration over how antibiotics are used in this country--specifically,
how farmers use them to promote the growth of livestock.

Experts have long known that the overuse of antibiotics by doctors and
their patients has reduced the ability of those drugs to cure infections.
Now there is mounting evidence that the antibiotics widely used on farm
animals are also diminishing the power of important antibiotics to help
people.

Giving animals antibiotics in their feed can cause microbes in the
livestock to become resistant to the drugs. People can then become infected
with the resistant bacteria by eating or handling meat contaminated with
the pathogens.

"Many of us believe there is a tremendous overuse of antibiotics for
animals," said Marcus Zervos, an infectious disease specialist at William
Beaumont Hospital in Royal Oak, Mich., who was involved in the Michigan
case. "There is some very strong opposition to our view that animal
antibiotics are undermining antibiotics for people, but this whole area has
to be reconsidered."

Most of the antibiotics used on the farm are not administered to treat sick
animals. Instead, farmers feed livestock a low-level diet of antibiotics to
attack bacteria that might require the animal's body to expend energy to
kill off. This allows animals to grow more quickly and, from a producer's
point of view, more efficiently.

But this practice has increasingly become the focus of concern. Researchers
have already found evidence that the use of antibiotics on farms has led to
an increase in antibiotic-resistant cases of food poisoning caused by
campylobacter and salmonella bacteria in people.

Now, doctors and researchers point to the antibiotic the Michigan woman
received--Synercid, an important drug-of-last-resort in fighting
life-threatening infections--as a case study illustrating why they are so
concerned.

While Synercid was approved for human use only last fall, a closely related
drug called Virginiamycin has been used on livestock since 1974.
Researchers have found Virginiamycin-resistant bacteria in as much as 50
percent of supermarket chicken, turkey and pork. That alone causes concern
that the effectiveness of Synercid is already significantly reduced in humans.

"It's clear that the use of Virginiamycin to promote the growth of food
animals is a hazard to human health," said Frederick J. Angulo of the
federal Centers for Disease Control and Prevention (CDC). "It's difficult
to track the chain of evidence we need to say for certain that the
Virginiamycin in animals results in resistance to Synercid in humans. But
we do believe the seeds for Synercid-resistant [bacteria] were planted on
the farm, and are likely to blossom in hospitals."

Defenders of animal antibiotics say the scientific evidence linking
Virginiamycin resistance in animals to Synercid resistance in humans
remains inconclusive, and that animal antibiotics in general pose no
immediate danger to people. Studies have found Synercid resistance in 1
percent to 4 percent of humans tested, they point out, and that is far
below the rate of Virginiamycin resistance found in animals.

"We're not at all convinced, based on the data, that Virginiamycin is the
cause of the Synercid resistance, however minimal, in the human
population," said Carl Johnson of Pfizer Inc., which developed
Virginiamycin and later sold the rights to Synercid to Aventis
Pharmaceuticals. "We believe it is coming from hospital use."

Others see a need for immediate action. In Europe, officials have already
banned the farm use of Virginiamycin and three other growth-promoting
antibiotics, following recommendations from the World Health Organization.
Legislation to impose a similar ban in the United States was introduced in
Congress last year by Rep. Sherrod Brown (D-Ohio). And consumer and public
health groups petitioned the FDA last year to stop the use of any drugs
used as animal growth promoters that are also used to treat diseases in
people.

In response, the FDA is trying to fully understand and quantify the risk to
humans posed by antibiotic use in animals, and will undertake a formal risk
assessment of Synercid and Virginiamycin this spring.

"Experts are saying they're seeing resistance to Synercid, and that it must
be coming from the animal use of Virginiamycin," said Sharon Thompson of
the FDA's Center of Veterinary Medicine. "That is exactly the concern we
are looking at. We're collecting information now and there will be a
thorough review."

More than a year ago, the FDA proposed new guidelines to limit the spread
of antibiotic resistance, and late last year claimed authority to require
drug companies to prove any new animal antibiotics won't dangerously
increase antibiotic resistance in humans. In the future, FDA officials
said, the agency will also review some animal antibiotics already on the
market, and will require new testing and new standards for those closely
related to vital human antibiotics.

The FDA's actions have left drugmakers and livestock producers worried and
angry. They say that animal antibiotics have been safe and very useful for
decades, and that farmers need them to keep their animals healthy and
growing as fast as they can. Without them, American meat and poultry would
not be as safe from disease-causing organisms, and prices would rise as
well, they say. And they complain that the FDA has already imposed a "de
facto moratorium" on new animal antibiotics while the proposed guidelines
are debated.

The FDA "is adding new requirements for resistance information never asked
for in the past, and almost impossible to actually gather now," said
Richard Carnevale of the Animal Health Institute, which represents
pharmaceutical companies that supply farm drugs.

"In essence, we can't get products approved because we can't learn what we
have to prove," he said. "One company has been working for more than a year
on a protocol [to test antibiotic resistance], and the FDA is never
satisfied and just tells them to keep tweaking."

Carnevale asserted that the FDA slowdown in animal antibiotic approvals has
discouraged drug companies from investing in the costly development of new
antibiotics for humans, too.

Livestock growers also are fighting efforts to limit antibiotic use. They
consider the medications essential to their business, and are rushing as
well to protect the FDA from what they consider to be nonscientific
influences.

"Unlike Europe, we want to make sure decisions are based on science alone
here," said Gary M. Weber of the National Cattlemen's Beef Association. "At
this point, we don't see any evidence of an identifiable problem regarding
antibiotic resistance from animal feed. And in the absence of good science
showing that, we think it would be a real blunder to ban or limit its use."

The European Union asserts that governments can take action when they
believe a health danger is present, even if it cannot be scientifically
proven at the time. But the U.S. Trade Representative has opposed the
ban--supporting the U.S. industry position that the risks of animal
antibiotics have not been scientifically assessed--and has threatened to
take its case to the World Trade Organization.

Researchers agree that many aspects of antibiotic resistance remain
unresolved. But they say that more precise methods of studying bacteria on
the molecular level have recently allowed them to demonstrate that
resistant forms of at least two common bacteria--campylobacter and
salmonella--are being passed from animals to humans. These organisms have
become increasingly resistant to antibiotics known as
fluoroquinolones--which include the most widely used antibiotic to treat
food-borne infections, Ciprofloxacin.

Researchers found that chicken treated with fluoroquinolones were being
colonized by campylobacter bacteria resistant to the drug, and that those
bacteria were being passed to humans. An FDA-commissioned risk assessment
concluded in December that at least 5,000 Americans will suffer longer
bouts of campylobacter food poisoning annually because of fluoroquinolone
resistance passing from chicken to people.

The threat from Synercid-resistant bacteria is potentially greater, because
the drug generally is used to control infections when a patient's immune
system is already severely compromised--during organ transplants and
chemotherapy, for instance. But the pathway from Virginiamycin resistance
in animals to Synercid resistance in humans is more complex than with
campylobacter or salmonella.

Virginiamycin in feed produces resistance in bacteria called enterococci,
which inhabit the intestines of humans and animals. They generally do not
cause disease, and so there is no inherent risk involved with their
development of antibiotic resistance. They can, however, become very
dangerous if their resistance transfers to other enterococci that inhabit
human wounds, catheter infections and other hospital-acquired contagions.
Synercid was approved to attack a dangerous form of enterococci resistant
to the antibiotic that used to be doctors' last resort, Vancomycin.

Researchers believe that animal resistance to Virginiamycin is appearing as
Synercid resistance in those now very dangerous enterococci. But the
scientific debate over this is fierce, and the newest scientific methods
have not conclusively traced Synercid resistance in humans from
Virginiamycin resistance in animals.

"The Synercid story is just starting to play out," said J. Glenn Morris of
the University of Maryland in Baltimore, a specialist in the field. "We
know we have a major problem on our hands in terms of antibiotic resistance
in our hospitals. The question about Synercid is whether we'll act to
protect it now, or just accept the risk that it and other important
antibiotics may become ineffective sooner because of this animal use."

Drugs in the Food Chain

Farm animals treated with low levels of antibiotics are developing
drug-resistant forms of bacteria, posing potential health risks in humans.

Resistant infections

Researchers are concerned that animals fed the antibiotic Virginiamycin are
passing along antibiotic-resistant forms of enterococci (shown) to humans.

Possible health risks
Food poisoning

Bacteria from farm animals, such as salmonella and campylobacter, have been
causing antibiotic-resistant cases of food poisoning in people.
SOURCE: Centers for Disease Control and Prevention

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