Eliminate nontherapeutic antimicrobial use in agriculture: AMA

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Diversifying its crusade against misuse of antimicrobials and consequential resistance, the American Medical Association most recently set its sights on animal agriculture.

In a resolution adopted June 19 by its House of Delegates, the AMA opposed the use of antimicrobials at "non-therapeutic levels" in agriculture or as pesticides or growth promoters.

The AMA resolution urges "that non-therapeutic use in animals of antimicrobials (that are also used in humans) should be terminated or phased out based on scientifically sound risk assessments. ..."

In the resolution, the AMA does not define the term "non-therapeutic."

The Animal Health Institute, the U.S. trade association that represents manufacturers of animal health care products, criticized the AMA resolution as "far too broad and sweeping" and an ineffective solution to addressing antimicrobial resistance. However, AHI vice president of public affairs, Ron Phillips, acknowledged that this amended form of the resolution includes two improvements—addition of the phrases "that are also used in humans" and "based on scientifically sound risk assessments."

"Those are very pregnant words," Phillips said. "Of course, we don't believe the [fluoroquinolone] risk assessment performed by the Center for Veterinary Medicine was a sound risk assessment, so there's a lot of terminology where beauty is in the eyes of the beholder. But those two phrases certainly are improvements."

According to the AHI, the majority of antimicrobials used for disease prevention or growth promotion fall into two categories—one, they are arsenicals or ionophores, which have no use in human medicine, or two, they constitute antimicrobials such as bacitracin and tylosin, which public health agencies have not associated with human resistance problems.

J. Edward Hill, MD, a family practitioner in Tupelo, Miss, and chair-elect of the AMA board of trustees, said, "If that is true [about arsenicals or ionophores], then the AMA resolution should have no consequence for the [the AHI], because it very clearly states [that nontherapeutic use in animals should be terminated or phased out for antimicrobials] 'that are used in humans.'"

In contrast, the AMA is concerned about the second category—any antimicrobial use in animals that may result in resistance to an antimicrobial that is used in humans. For example, there are some data to show that tylosin may result in erythromycin resistance in humans, even though tylosin is never used in humans.

If phasing out an antimicrobial would result in unsafe foods—a consideration the AHI and AVMA have raised—then the AMA is in favor of a risk assessment to balance the potential for antimicrobial resistance with the possibility of foodborne disease resulting from less-healthy animals.

The FDA is supportive of the AMA resolution; in fact, the revision is similar to the version the FDA-CVM recommended to the AMA House of Delegates. The FDA did not agree with the approach of the original resolution—that antimicrobial use simply be banned at less than therapeutic levels in agriculture. In the agency's perspective, the critical issue is whether a given antimicrobial also has a use in human medicine, and that any judgments on whether to take action regarding that drug should be based on scientific evidence and associated risk.

The AMA embraced the resolution despite the association's awareness that the veterinary profession has developed general and species-specific judicious use guidelines. "We think it's great [the veterinary profession is] addressing this issue," Dr. Hill said, "but our general position is that using antibiotics as prophylactics for disease prevention is something that's going to have to be looked at a little closer."

Why has the AMA turned its attention toward agricultural use?

"This is not necessarily the opinion of the AMA," Dr. Hill said, "but a lot of physicians will tell you that we acknowledge the fact that human medicine will generate antibiotic resistance. The issue is that if you allow resistance to start somewhere else, it can get magnified and amplified in the human treatment system. Therefore, the precaution should be that you cannot allow resistance to start outside.

"If [an antimicrobial] is used in humans and it is the therapy of last resort, then it's a major issue for physicians."

According to Dr. Hill, organized medicine is trying to do its part to stem antimicrobial resistance. "We're fully aware that a lot of it starts at home."

The American Academy of Pediatrics and the 150,000-member American College of Physicians have strong guidelines covering indications for antimicrobial use and which ones to consider for each indication. In its 2000 study on antimicrobial use in human medicine, the ACP found that the most abuse occurs when treating upper-respiratory-tract infections. Its guidelines now state that for most upper-respiratory-tract infections, physicians should not prescribe antimicrobials. Instead, the ACP advises "watchful waiting."

"That's a very powerful statement to come from them," Dr. Hill said.

At present there is no surveillance to see how the voluntary guidelines are being followed. Monitoring is a sensitive issue because of privacy/confidentiality and liability concerns.

Some surveillance may be initiated, however, under another provision of the AMA resolution—that the AMA will work with other organizations to establish a national program to counter antimicrobial resistance in clinical practice similar to the California Medical Association Foundation AWARE program.

AWARE (www.aware.md) is an educational feedback-based program to ensure that physicians are aware of antimicrobial use guidelines, that they use them in their practice, and that a feedback method be provided on usage. The AMA envisions working with the American College of Physicians, American Academy of Pediatrics, Alliance for the Prudent Use of Antibiotics, and other organizations.

The AMA resolution also urges that increased surveillance of antimicrobial use and resistance be funded and instituted as recommended by the Institute of Medicine and American Society of Microbiology.

Because the National Antimicrobial Resistance Monitoring System is already doing surveillance of resistance patterns in foodborne pathogens, the AMA plans to compare the NARMS effort with the IOM and ASM recommendations, and if necessary, to ask the CDC to expand its surveillance network or the elements being surveyed.

Another AHI contention is that the AMA resolution's usage estimates are unsupportable. From its 1999 survey of sales of its members, the AHI estimates that of about 20 million pounds of antimicrobials used in animals, only 2.7 million are used for growth promotion. This contrasts with the number cited in the background to the AMA resolution-16 million pounds for growth promotion and prophylactic use.

Debate over the volume of usage, however, skirts the real issue: what is the impact of "non-therapeutic" antimicrobial use on human or animal health or welfare?

The AHI cited the results of a survey of experts in human infections in the United Kingdom and elsewhere, which indicated that animal sources might account for as little as 3.88 percent of the human antimicrobial resistance problem. The survey results were published last year as a letter to the editor in the Journal of Antimicrobial Chemotherapy (Vol. 46, pages 643-645).

Moreover, the amount of antimicrobials used in animals is not an indication of their contribution to resistance development in humans, the AHI contends. Virginiamycin, a streptogramin antimicrobial, has been used for more than 30 years in animal feed. Yet at the time the first human streptogramin was approved, the resistance in humans was "exceedingly low," according to the institute.

That is why the risk assessment is so important. But Dr. Hill noted that public health officials, including those at the national Centers for Disease Control and Prevention, are concerned that the process is taking much longer than it should, and antimicrobial resistance can develop quickly. Over the past three years, the only risk assessment completed has been the controversial one on fluoroquinolones in poultry.

"The question, then, is that if we keep waiting on this issue," Dr. Hill said, "will it, at some point, be too late?"