It's too bad they don't make a life preserver for the spin zone because that's just where the war over antibiotics in agriculture will take you. The debate comes complete with confusing terms and definitions, no clear estimates of actual antibiotic use in food animals, conflicting scientific evidence and politics to boot.

Still, no matter how you view the antibiotics issue, the momentum for some sort of restrictions on antibiotic use in agriculture seems to be gaining.

“We have substantial evidence now that resistant pathogens do form in treated animals and can be transmitted to humans through the food supply,” says Linda Tollefson, deputy director of the Food and Drug Administration (FDA) Center for Veterinary Medicine. “From a public health perspective, that risk has to be minimized.”

In September, the FDA released drafted “guidance” to the animal health industry. (See “FDA Offers Industry Guidance,” page 30.) Not a formal rule, this proposal would require makers of a proposed animal antibiotic to assess whether use of the product in animals could encourage the growth of disease-causing bacteria resistant to antibiotics used in human medicine.

“The draft lays out quite vividly that we consider this a very serious issue,” Tollefson says.

The FDA actions follow related developments in Congress earlier this year. Legislators are considering two almost identical proposals — one in the House and one in the Senate — that would restrict routine feeding of medically important antibiotics to farm animals. (See “Animal Drug Bills In Congress,” page 32.) Both bills would phase out the non-therapeutic use of eight types of antibiotics in animal agriculture, including penicillins, tetracyclines, macrolides, lincomycin, bacitracin, virginiamycin, aminoglycosides and sulfonamides.

A Wake-Up Call

These bills are an ill-informed political solution to a scientific problem, says Mike Apley, DVM, of Iowa State University. “The fact that they are even in Congress should really grab our attention,” he says.

For starters, the people who put forth the bills have a very limited understanding of all the concepts involved in showing something is or is not a problem with resistance, Apley says.

“Absolute definitive proof of cause and effect between food animal use and human therapeutics would be very difficult at this time,” he says.

Instead, these bills put the emphasis on the sponsors of a drug to prove a negative — that a product isn't causing a resistance problem in humans. Furthermore, they really don't define how a drug would be proven safe, Apley says. Manufacturers would have no criteria and a very limited time to prove anything.

“Trying to prove a negative without any standards is an impossibility,” he says.

Behind The Legislation

One of the key players behind the bills is a coalition called Keep Antibiotics Working (KAW). Its primary objective is to end, what it calls, the “overuse and misuse” of antibiotics in animal agriculture. Participants include groups like the Center for Science in the Public Interest (CSPI), Environmental Defense (ED), Institute for Agriculture and Trade Policy, Sierra Club, Union of Concerned Scientists and the Waterkeeper Alliance.

“It's important to understand that we aren't talking about ending all agricultural use,” says Karen Florini, a coalition spokesperson and ED attorney. “You could still use them for treatment of sick animals, but not non-therapeutically.”

That sounds simple enough, but a lack of clear and consistent terms and definitions makes this debate complex. There's non-therapeutic use, routine use, prophylactic use, growth-promotant use, sub-therapeutic use, and disease prevention — just to name a few.

Neither of the bills KAW is backing offers an adequate definition of the antibiotic use they want to curtail, Apley says.

“If you just start calling everything ‘sub-therapeutic’ without a definition applied to it, then all of a sudden, it becomes a problem,” he says. “I look at the strictly growth-promotant use and the use that has a disease prevention or suppression purpose as entirely different things. They (those behind the legislation) don't seem to differentiate.”

Florini admits drawing a clear distinction between prophylactic use and other uses can be difficult. Still, KAW is very critical of livestock producers and convinced some producers would prefer to throw antibiotics at problems rather than address them through management.

“We're against routine, every flock, every herd prevention,” explains Tamar Barlam, MD, another KAW spokesperson who works for CSPI. “That's the routine use for which they (the animal health industry) are using the term ‘disease prevention.’ But they are really just giving it to every single animal that goes through a particular farm.”

Barlam says if a veterinarian looks at a group of animals and identifies a disease risk in the herd, then those animals should be treated. But what often happens, she adds, is producers or veterinarians say, “Gee, with all these animals so close together, disease is going to happen. Therefore, every animal needs to be treated with an antibiotic.”

KAW's position is that you can't provide for human health and use antibiotics in food animals for anything other than direct individual animal therapy of ill animals, Apley says. That concerns him.

“As a veterinarian, I take exception to that,” he says, “because I can have a benefit on disease incidence and disease severity by judicious, targeted application of animal antimicrobials early in or immediately prior to a suspected outbreak.”

Apley says he's frustrated that people behind the legislation likely have no understanding of modern agriculture. He wonders how many of them have seen modern beef production techniques.

“If they think they're going to force us to do more research and work on preventive programs by taking away the tools with which we address these disease outbreaks, I've got news for them,” he says. “We're already doing all of that.”

Controlling disease and the economics of drug costs are already major issues for beef producers, he says.

“To economize on the use of antimicrobials means preventing disease by other means,” Apley says. “We've got a very aggressive vaccine industry and also retained ownership and integrated marketing programs that are coordinating preventive programs much earlier in the animals' lifetimes to engender immunity. Nutrition and genetic selection for disease resistance are also major initiatives.”

For perspective, it costs producers about $2 to vaccinate a calf two or three times prior to big stresses. Compare that to the $15 to $20 it costs to treat an animal with antimicrobials if it gets sick.

“We're not too keen on just trying to medicate our way through it,” he explains.

Ignored Evidence?

Another target of KAW's criticism is animal drug makers, whose defensive tactics Florini tries to equate with those of the tobacco industry. The implication is that the animal health industry, which likely would feel the first effects of any ban on sub-therapeutic antibiotic use, is ignoring the scientific evidence on the problem.

But the Coalition for Animal Health (CAH), which includes the American Veterinary Medical Association and the Animal Health Institute (AHI), says it's committed to maintaining the efficacy of antibiotics for human and animal medicine. CAH says judicious use of antibiotics to protect animal health and to minimize pathogens is a vital part of providing a safe and healthy food supply for American consumers.

CAH's position is that “theoretical risk of public health being impacted by animal antibiotic use is not a real risk, and the potential of it becoming a real threat is diminishing.” Thus, CAH opposes the current legislation to restrict antibiotic use in agriculture, calling the bills a “simplistic solution” and contending such legislation overrides FDA's authority and “puts politics ahead of science.”

In September, AHI reported that the human health risk of antibiotic use in food animals is extremely small. That's according to an independent group of human microbiologists, risk assessors, veterinarians and animal health experts.

The group concluded that while the use of antibiotics in humans and animals undoubtedly leads to resistance, and while some resistant organisms reach humans via the food chain, little additional harm results from resistance — even when infection occurs.

“In 50 years of antibiotic use in animals and man, the development of resistance in animals has not made a major impact on human and animal health, and such a development seems unlikely to happen overnight now,” says Ian Phillips, MD, who chaired the group.

AHI also reports that antibiotic use in animals is declining, according to a recent survey of its members. (See Table 1.)

Even so, Apley says he's not sure either side in this debate is non-biased.

“I think antimicrobial use in animals can lead to development of resistance in some bacterial populations. But if we aren't careful, draconian control measures may carry through to control measures that adversely affect both animal and human health,” he says.

Possible Consequences

This legislation is really about “clear and compelling scientific evidence” that indicates the non-therapeutic use of medically important antibiotics needs to end, Florini says. Barlam concurs, adding that eliminating routine antibiotic use in livestock would benefit public health because bacteria that are more sensitive to antibiotics could then come back and repopulate.

But Apley isn't so sure. “It's naïve to think all those problems would go away by removing certain antimicrobial uses from food animals,” he says.

Phillips' group concludes that banning any antibiotic usage in animals, in the absence of a full risk assessment, is not useful and could even be harmful to both human and animal health.

So how would banning the preventive use of antimicrobials in animal agriculture impact beef producers? The cattle industry would certainly survive, Apley says, but the control of respiratory disease in higher-risk types of cattle would be severely limited. The effect, he says, would be at least a short-term increase in therapeutic use of antimicrobials and an increase in cattle fatality.

The Take Home

Florini says KAW's mission isn't about “being mean to farmers.” Barlam adds that the beef industry needs to recognize a growing consensus among healthcare professionals that routine use in animals is not a good use of medically important antibiotics.

“This isn't just a few groups or a few environmental groups,” she says. “We're getting a growing list of really respected healthcare professionals who are concerned about this as a public health issue.”

Apley agrees. The issue is important to beef producers because the misuse of antimicrobials in food animals could cause a problem for public health. But this must be put in perspective with other sources of resistance problems in human medicine, and legislating a short-cut deal designed to enhance other agendas is not the answer, he says.

“In defense of our industry, I think we're working hard to improve non-antimicrobial intervention strategies,” he says. “And we can continue to focus on some of the things we are already doing.”

Likewise, Phillips says efforts should instead focus on reducing the transmission of all food-borne pathogens regardless of their antibiotic susceptibility.

“This can only occur through insistence on good hygienic practices on farms, in abattoirs, during distribution and marketing of food, and in the proper handling and cooking of food,” he says. “And it must be accompanied by consumer vigilance.”

FDA Offers Industry Guidance

New regulations that could limit the development of new animal drugs are being considered by the Food and Drug Administration (FDA). The agency has the authority to protect human health by removing products from the market when they present a risk to public health.

A draft guidance it released in early September represents FDA's current thinking on the antibiotics issue. It recommends an approach for assessing the safety of new antimicrobial drugs for animals with regard to their microbiological effects on bacteria of human health concern. An alternate approach may be used as long as it satisfies the requirements of applicable statutes and regulations.

The guidance would for the first time require the maker of a proposed animal antibiotic to assess whether use of that product in animals could encourage the growth of disease-causing bacteria that are resistant to antibiotics used in human medicine.

If a drug is too similar to an important antibiotic for people, for instance, it could be kept off the market. Currently, the drug maker has to show only that it doesn't leave any residue in meat.

The animal drug industry has welcomed the guidance, in part because it avoids more aggressive solutions to the problem of antibiotic resistance. But the Animal Health Institute's (AHI) position is that advocates exaggerate the hazards of animal antibiotics to human medicine.

AHI, which represents animal drug companies, calls some details of the proposal “unnecessarily stringent” and says it “will make it very difficult for new antibiotic products to be approved.”

To download or read the 50-page draft online, visit www.fda.gov/cvm.

All comments and suggestions about the draft must be submitted by Nov. 27 and should be identified with the Docket No. 98D-1146.

To comment, write to: Dockets Management Branch (HFA 305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. Or submit comments electronically through www.accessdata.fda.gov/scripts/oc/dockets/commentdocket.cfm.

For more information, contact William T. Flynn at the FDA's Center for Veterinary Medicine at 301/827-4514 or by e-mail to wflynn@cvm.fda.gov.

Animal Drug Bills In Congress

Senate bill: Preservation of Antibiotics for Human Treatment Act (S.2508); sponsored by Sen. Edward Kennedy (D-MA); introduced May 13, 2002

Description: To begin phase out of “routine” feeding of medically important antibiotics to healthy farm animals

Latest major action: Referred to Senate committee on May 13, 2002; read twice and referred to the Committee on Health, Education, Labor and Pensions

House bill: Preservation of Antibiotics for Human Treatment Act (H.R.3804); sponsored by Rep. Sherrod Brown (D-OH); introduced Feb. 27, 2002

Description: To amend the Federal Food, Drug and Cosmetic Act to ensure that use of certain antibiotic drugs in animal agriculture doesn't compromise human health by contributing to the development of antibiotic resistance

Latest major action: Referred to House subcommittee on March 13; referred to the Subcommittee on Health.

For the text of these bills or status updates, visit the Library of Congress online at http://thomas.loc.gov.