Curtailing Antibiotics Use in Agriculture

It is time for action: this use contributes to bacterial resistance in humans  

Steve Heilig, MPH, Philip Lee, MD, and Lester Breslow, MD

Antibiotics are arguably the single most important and widely used medical intervention of our era. Almost every medical specialty uses antibiotics at some point. These drugs have prevented incalculable suffering and death, and are perhaps still the closest medications we have to a "magic bullet."

Of course, bad bugs can bite back, and bacterial adaptation and resistance was reported very soon after antibiotics were first used.   The struggle to stay one step ahead of pathogens has been widely described and debated.  Correcting the overuse of antibiotics in human medicine has gradually become a priority, with slow but heartening progress being gained in this Darwinian race.  Still, the rise of multi-drug resistance and the ready transfer of resistant traits among pathogens require heightened action if we are to prevent increasing outbreaks of infections which become more difficult, or even impossible, to treat.

One essential course of action is to minimize any and all causes and reservoirs of antibiotic resistance.   Besides medical use in humans, there is the troubling issue of use in agriculture, specifically livestock production.  Antibiotics have long been routinely used not only for treatment of infections, but also as a means of getting animals to market faster via growth promotion. Controversies about these practices have resulted in numerous reports, dating back decades, urging more caution or outright bans on the practice.  The World Health Organization and other leading medical and public health bodies have advised that animals not be dosed with antibiotics used in humans‹to little avail here in the United States to date, even though our own Food and Drug Administration took this position as far back as 1972. [1]

Still, many longtime observers of the issue were surprised‹or even shocked‹to learn the true extent of antibiotic use on farms.   A recent report estimates that upwards of 70% of all antibiotics manufactured are used in agricultural settings. [2] While the exact percentages are uncertain, it appears that agricultural antibiotic use is much more substantial than previously thought.  And the type of use is worrisome, since it involves continual, sub-therapeutic doses that would seem to provide ideal environments for the selection of resistant pathogens.

The advent of new molecular epidemiological tools has heightened the worry, because these tools have been used to show that resistant bacteria originating on farms are finding their way into humans. [3-10] The extent of this epidemiological "spill-over" to date is uncertain‹assertions of the extent of bacterial resistance arising from farms vary widely‹and this needs to become a higher research priority.   But there is no question that the phenomenon does exist.

Recognizing this risk, the American Medical Association's house of delegates adopted a policy stating that the association "urges that non-therapeutic use of antimicrobials in animals that are also used in humans should be terminated or phased out based on scientifically sound risk assessments."[11] Reaction from the pharmaceutical industry, in the guise of a trade association of manufacturers of animal drugs, was swift. The Animal Health Institute (AHI) erroneously claimed that "The assertion that there is increasing evidence that resistance developed in animals is spreading to humans is not true," and it went on to oppose any further restriction on agricultural use.[12]

As a case study of such profit-motivated opposition, Bayer Corporation vigorously contested the Food and Drug Administration's proposal to withdraw one widely used class of antimicrobial, fluoroquinolines, from agricultural use.   These medications are only used therapeutically in agriculture, but they are used to combat some of the same bacterial pathogens that are treated with the same drugs in human medicine.  Hence there is a high risk of resistant strains finding their way from animals to humans. [13]  Abbot Laboratories, the other major manufacturer of fluoroquinolones, showed admirable scientific judgment and corporate responsibility in agreeing to the FDA's request.  Unfortunately, judging from the AHI's response to the AMA, we fear the drug industry's reactions may more closely mirror Bayer's shortsighted approach. Notably, even some forward-thinking agricultural leaders are now questioning the wisdom of such stonewalling. [14]

Admittedly, we tend to give more credibility to those who do not have any financial interest in the status quo.  Leading experts unequivocally state that our current practices of feeding antibiotics to animals goes against "a strong scientific consensus that it is a bad idea", and that the long stalemate on this issue constitutes a "struggle between strong science and bad politics." [15] The intentional obfuscations of the issue by those with profit in mind is an uncomfortable reminder of the long and ongoing battle to regulate the tobacco industry, with similar dismaying exercises in political and public relations lobbying and even scandal. [16] As with tobacco control, science and health concerns to should take precedence over profit in regulating the overuse of antibiotics in the production of meat and other agricultural products.

Antibiotics do have a place on farms, but the benefits of their use can likely be preserved while minimizing harm.   We do need to learn more about the extent of risk, but the delay tactic of allowing current practices to continue while "more research" is conducted is unacceptable.  Enough is already known to justify a more cautious, preventive approach.[17]  Other nations are ahead of the United States in this regard, and have banned routine agricultural use with demonstrable benefit in terms of reduced bacterial resistance [18].

We call on the FDA or legislators to, in the coming year, ban non-therapeutic agricultural use of antibiotics.   This ban should only be lifted if it is scientifically proven, in unbiased studies, that this use does not contribute to bacterial resistance in humans. Producers of agricultural antibiotics should be required to submit data on the specific antibiotics used, in sufficient detail to track usage and resistance trends.

Bayer should reverse its opposition to the ban on fluoroquinolines. Finally, individual and business consumers of meat should begin to demand that the meat they purchase be grown without routine use of antibiotics.

With newly heightened concerns about the threat of biological terrorism, including the potential use of infectious agents, the need to preserve the efficacy and supply of our antibiotic tools becomes even more crucial.   It is time for our government to act in the public interest on this important issue.

Steve Heilig, MPH, is on staff at the SFMS,   Philip Lee, MD, is a Professor of Social Medicine (Emeritus) at the Institute of Health Policy Studies, University of California, San Francisco, and Lester Breslow, MD, is a Professor and Dean Emeritus at the School of  Public Health, University of California, Los Angeles.

This article originally appeared in the Western Journal of Medicine in January 2002

For information on the growing campaign surrounding this issue, see:

http://www.keepantibioticsworking.com

References

1.  World Health Organization.  Press Release WHO/39 11 September 2001.  WHO Acts to Safeguard Vital Treatments for the Future. Available at http://www.who.int/inf-pr-2001/en/pr2001-39.html. Accessed September 19, 2001.

2.  Union of Concerned Scientists (Mellon M, Fondriest S).  Hogging It: Estimates of Animal Abuse in Livestock.  Nucleus 2001;23(1):1-3

3.  Witte W.  Medical consequences of antibiotic use in agriculture. Science 1998;279:996-997

4.  Ferber D.  Antibiotics on the hoof?  Science 2000;288:792-794

5.  Alliance for the Prudent Use of Antibiotics (Tufts University). Annotated Ecology References.  Available at http://www.healthsci.tufts.edu/apua/Ecology/annotRef.html#animals. Accessed Sept. 19, 2001.

6.  Van den Bogaard AE, London N, Driessen C, Stobberingh EE, et al. Antibiotic resistance of faecal Escherichia coli in poultry, poultry farmers and poultry slaughterers. J Antimicrob Chemother 2001 47: 763-771

7. Van Looveren M, Daube G, De Zutter LJ, et al. Antimicrobial susceptibilities of Campylobacter strains isolated from food animals in Belgium. J Antimicrob Chemother 2001;48: 235-240

8.  White DG, Zhao A, Sudler R, et al.  The isolation of antibiotic-resistant salmonella from retail ground meats.  N Engl J Med 2001;345:1147-54

9.  McDonald LC, Rossiter S, Mackinson C, et al. Quinupristin-dalforpristin-resistant enterococcus faecium on chicken and in human stool specimens.  N Engl J. Med 2001;345:1155-60

10.  Sorensen TL, Blom M, Monnet DL, et al. Transient intestinal carriage after ingestion of antibiotic-resistant enterococcus faecium from chicken and pork.  N Engl J Med 2001;345:1161-6

11.  American Medical Association.  Antimicrobial use and resistance. House of Delegates resolution 508 (A-01), June, 2001.  Available at http://www.keepantibioticsworking.com/library/uploadedfiles/American_Medical_Association_Resolution_508_-_.htm.  Accessed October 12, 2001

12.  Animal Health Institute.  Statement on AMA resolution on agricultural antibiotics.  June 20, 2001

13.  Olsen SJ, Debess EE, McGivern BS, et al.  A nosocomial outbreak of fluorouinoline-reistant salmonella infection.  N Engl J Med 2001:344:1572-1579

14.  Richardson L.  Animal agriculture's BSOD.  California Farmer 2001;284(11):6

15.  Falkow S. Kennedy D.  Antibiotics, animals, and people - again! Science 2001; 291:397

16.  Marshall E.  Scientists quit antibiotics panel at CAST.  Science 1979;203:732-733.

17.  Kriebel D, Tickner J.  Reenergizing public health through precaution.  Am J Public Health  2001;91:1351-1354

18.  Aarestrup FM, Seyfarth AM, Emborg H-D et al. Effect of abolishment of the use of antimicrobial antibiotics for growth promotion on occurance of antimicrobial resistance in fecal enterococci from food animals in Denmark.  Antimicrobial Agents and Chemotherapy 2001;45:2054-2059