In the mid-1970s, I was asked by the Animal Health Institute to propose a study which would address the possible human health consequences of providing antibiotic-laced feed to farm animals. The resulting prospective study (Levy et al., 1976) examined the effects of providing subtherapeutic levels of an antibiotic as a growth promoter to animals on the intestinal flora of people and animals.
We raised 300 chickens from the day of hatching to full-grown hens and roosters, placed them in cages, and fed half oxytetracycline-laced feed and the other half antibiotic-free feed. Over the next six months, we examined weekly fecal samples from the chickens and from members of the farm family, as well as from a control group of neighbors with children attending the same schools as the farm children.
Within 36 hr, those chickens fed subtherapeutic levels of oxytetracyline began to excrete tetracycline-resistant Escherichia coli and eventually E. coli resistant to other antibiotics. The flora of the control group did not change.
This emergence of multidrug resistance following prolonged use of a single antibiotic in chickens mimicked a finding in people reported previously by investigators in England.
Our study also showed the emergence of drug-resistant E. coli in the intestinal flora of farm dwellers, but not the neighbors, and the spread of resistant E. coli strains from chickens to farm workers. Our study is the only prospective study which documents such a change on a farm following the introduction of an antibiotic in feed.
More studies and events in the 1980s led to increased concern over the effects of animal use of antibiotics on human health. Bates et al. (1994) found vancomycin-resistant enterococci (VRE) among animals on a United Kingdom farm. This finding was later linked to the use of a vancomycin-like drug, avoparcin, as a feed additive. This report and the subsequent finding of VRE in other animals, farm workers, and the ambulatory population led the European Union six years ago to ban all antibiotics for growth promotion. Subsequent to the avoparcin removal, there was a dramatic drop in the levels of VRE in animals and people. In the United States, however, despite the urging by microbiologists and clinicians to remove the growth-promotant practice, it continues to this day.
The increasing possible health crisis posed by multidrug resistance globally has led to renewed scrutiny of how antibiotics are used in man, animals, and agriculture. The Food and Drug Administration’s Center for Veterinary Medicine recently banned a fluoroquinolone, enrofloxacin, from use in poultry, following a demonstrated association between its use and the appearance of fluoroquinolone-resistant Campylobacter among the animals. This was the first time FDA has succeeded in removing an antibiotic based on its effect on the bacteria associated with the animals and the spread of drug-resistant bacteria from animals to people.
FDA’s evaluation and position on this therapeutic use has had an impact on other areas of animal use, as well. McDonalds in 2003, and the Compass Group more recently, announced that they will no longer buy meat products from suppliers who use antibiotics as growth promoters.
We are entering an era of new insights into antibiotic-associated impacts. While more-prudent use is urged in people, with many clinical professional groups working for this goal, there is great need to look at other applications, including animal husbandry and agriculture. In some instances, antibiotics are sprayed onto fruit trees to prevent infection, leading to a wide geographic spread of the antibiotic and the potential associated selection of resistant bacteria in its path. The Alliance for the Prudent Use of Antibiotics in 2002 issued a report recommending improved use of antibiotics in animals, including removal of growth-promotion use, and a careful examination of their uses in prophylaxis and treatment (Barza and Gorbach, 2002).
A more rational understanding of the consequences of antibiotic misuse has emerged in all areas of antibiotic use. It is hoped that this wave of rationality will stay strong, leading to improved antibiotic use and a decline in the environmental load of antibiotic-resistant bacteria.
by Stuart B. Levy, M.D., President of the Alliance for the Prudent Use of Antibiotics, is Professor of Molecular Biology & Microbiology and of Medicine, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111 ( [email protected] )
Barza, M and Gorbach, S.L. 2002. The need to improve antimicrobial use in agriculture: The APUA FAAIR report. Clin. Infect. Dis. 34(Suppl. 3).
Bates, J., Jordens, J.Z., and Griffiths, D.T. 1994. Farm animals as a putative reservoir for vancomycin-resistant enterococci infection in man. J. Antimicrob. Chemother. 34: 507-16.
Levy, S.B., FitzGerald, G.B., and Macone, A.B. 1976. Changes in intestinal flora of farm personnel after introduction of tetracycline-supplemented feed on a farm. New Eng. J. Med. 295: 583-588.