August 01, 2008

 

 AVMA cautions against indiscriminate broad bans on livestock antimicrobials - August 1, 2008

 posted July 15, 2008
 
AVMA cautions against indiscriminate broad bans on livestock antimicrobials
 

AVMA Assistant Executive Vice President Lyle P. Vogel told a Senate committee in June that wide-scale bans on approved uses of antimicrobials in food animals would hurt animals, do little to improve public health, and could, in fact, lead to an unsafe food supply.

The increase in antimicrobial-resistant pathogens—especially methicillin-resistant Staphylococcus aureus—has Congress searching for a remedy to a phenomenon that is rendering important infection-fighting drugs in human medicine less effective.

The Food and Drug Administration estimates that two million people acquire bacterial infections in U.S. hospitals annually, and 90,000 die as a result. About 70 percent of those infections are resistant to at least one drug.

Senator Sherrod Brown, who, in Sen. Ted Kennedy's absence, chaired the June 24 Health, Education, Labor and Pensions Committee hearing, described MRSA as a "wake-up call" for Congress to confront antimicrobial resistance. "Antimicrobial resistance can occur whenever antibiotics are used inappropriately—when doctors overprescribe, when patients don't understand the importance of taking their full course of therapy, when animals are fed antibiotics to maintain health rather than restore it, and when, in various ways, antimicrobials find their way into the environment," Brown said.

Efforts to use drugs prudently on farms are already under way. For example, the AVMA and allied veterinary organizations created judicious use guidelines starting in 1998. More recently, the pork industry established a Take Care—Use Antibiotics Responsibly program in 2005.

Some legislators are pushing for a ban on using antimicrobials as growth promotants, for feed efficiency, and for routine prevention of disease in animals if these antimicrobials are also used in human medicine. Kennedy is sponsoring one such measure, the Preservation of Antibiotics for Medical Treatment Act, a version of which is also being considered in the House.

The AVMA opposes Kennedy's bill for a number of reasons, mainly because it will restrict the use of antimicrobials to prevent or control disease in animals and because the Food and Drug Administration does not need new authority to safeguard public health. The process for evaluating food animal antimicrobials, the Association says, is at least as stringent, and often more so, than the approval process for human antibiotics.

Each food animal antibiotic undergoes an assessment for human, environmental, and animal safety as a part of the FDA's review. In 2003, evaluation of the potential to create antimicrobial resistance that may negatively impact human health was added as a requirement for approval of antimicrobials for food animals. The FDA is currently evaluating previously approved drugs, such as penicillins and tetracyclines used in feeds, under this new requirement.

Dr. Vogel, a veterinarian who has a master's in public health, explained the AVMA position at the hearing. He stated, "Because veterinarians are ethically charged with promoting public health in addition to protecting animal health and welfare, we participate in the prevention and control of both human and animal disease." When making decisions, veterinarians must balance the needs for public health and the needs for animal health and welfare.

He noted the Association's Guidelines for the Judicious Therapeutic Use of Antimicrobials. The guidelines, he said, were written with input from the Centers for Disease Control and Prevention, Department of Agriculture, FDA, and others to safeguard public health by stressing prudent and careful therapeutic use of antimicrobials.

Dr. Vogel also cautioned the senators against enacting seemingly simple solutions to address an extremely complex issue. "Passing legislation that would ban the use of these antibiotics before science-based studies and risk-based evaluations are done would be detrimental to animal and human health," he said. "Not all antimicrobials are equal in their probability of creating a risk to human health."

"Several risk assessments have been performed that demonstrate a very low risk to human health from the use of antimicrobials in food animals, and some of the models predict an increased human health burden if the use is withdrawn. Inappropriate reactions to the potential problem," Dr. Vogel continued, "could have unintended consequences that negatively affect animal health and welfare and, ultimately, could create other public health risks, such as increased foodborne disease."

The AVMA believes that the judicious and regulated use of antimicrobials through scientifically based FDA approvals and postapproval review provides sufficient protections for public health, Dr. Vogel added. Since 1996 in the United States, the case rate of human illness with multidrug-resistant Salmonella has had a relative decrease of 49 percent. Salmonella isolated from humans are half as likely to be resistant as they were in 1996. This information indicates that there is not a public health crisis related to human pathogens that are thought to originate in animals.

Using antimicrobials as growth promotants in food animals has been banned in Denmark since the late 1990s. In that time, Dr. Vogel said, there have been mixed results in terms of antibiotic resistance in humans. For example, resistance of Enterococcus isolated from humans to vancomycin stayed at 0 percent from 1997-2006 and may be related to the ban on the use of avoparcin (a drug never approved in the United States) as a growth promotant in animals.

There have, however, been dramatic increases in resistance to tetracyclines in treating Salmonella infections in humans, which may be related to the increased need to use tetracyclines to treat diseases in animals. Dr. Vogel also explained that the resistance of Enterococcus isolated from humans in Denmark to quinupristin/dalfopristin is 10 times higher than in the United States, despite the continued use of virginiamycin in the United States and the ban in Denmark. (Both virginiamycin and quinupristin/dalfopristin belong to the class of antimicrobials called streptogramins.)

"Passing legislation that would ban the use of these antibiotics before science-based studies and risk-based evaluations are done would be detrimental to animal and human health. Not all antimicrobials are equal in their probability of creating a risk to human health."

—DR. LYLE P. VOGEL,
ASSISTANT EXECUTIVE VICE PRESIDENT, AVMA

While the total quantity of antimicrobials used for all purposes in food animals in Denmark has decreased by 27 percent, the rise in disease prevalence has resulted in a 143 percent increase in the quantity of antimicrobials used for therapeutic purposes. And the antimicrobials now used more frequently are in classes that are also used in humans, such as tetracyclines.

"Evidence shows that the Danish ban, and a ban in the United States, if instituted, will cause animal health and welfare problems," Dr. Vogel said.

In addition to relieving pain and suffering, antimicrobials contribute to the public health by keeping animals healthy and preventing disease-causing bacteria from entering the food supply, Dr. Vogel said. A number of risk assessments indicate withdrawing virginiamycin, macrolides, and fluoroquinolones from food animals would put people at risk, he said.

New legislation is not the answer, according to Dr. Vogel. Increased surveillance through the National Antimicrobial Resistance Monitoring System—a multi-agency program monitoring for drug-resistant microbes in people, farm animals, and meats and other animal products since 1996—along with continued compliance with judicious use principles, may be sufficient to protect human health without compromising the health of food animals, he said.

In contrast, Jay P. Graham, PhD, a research fellow at the Johns Hopkins Bloomberg School of Public Health, told the senate panel that the effectiveness of antimicrobials is being squandered through inappropriate use in food animals.

"The method that now predominates in food animal agriculture—applying constant low doses of antimicrobials to billions of animals—facilitates the rapid emergence of resistant, disease-causing bacteria and compromises the ability of medicine to treat disease, making it clear that such inappropriate and indiscriminate use must end," Dr. Graham said.

But Dr. Vogel's testimony regarding resistance of presumably animal-origin bacteria sampled from humans shows a stable or decreasing trend instead of the "rapid emergence of resistant, disease-causing bacteria" theorized by Dr. Graham.

Another solution to the drug resistance problem is creating more antimicrobials. Infection-fighting drugs have a finite lifespan with limited financial returns, Barry I. Eisenstein, MD, senior vice president of Scientific Affairs at Cubist Pharmaceuticals, told the senators.

In addition, during the past decade, federal guidelines have made the approval process for new antimicrobials even more difficult, Dr. Eisenstein said. As a result, drug manufacturers are limiting research and development investments in anti-infectives, preferring instead to focus on more financially viable areas.

"The consequences of this lack of antimicrobial R & D have become devastating for patients, leaving us with increasing rates of antimicrobial resistance and fewer and fewer available therapies," Dr. Eisenstein said.

In a press release, Sen. Mike Enzi, the ranking member of the Senate committee, said Congress should consider expanding programs such as the FDA Orphan Products Grants Program that offer incentives to create new antibiotic treatments. "We simply aren't creating antibiotics fast enough," Enzi said.

To learn more about the AVMA's positions on antimicrobial use in livestock, visit www.avma.org and click on Issues, or visit the Association's food advocacy microsite, www.KeepOurFoodSafe.org.