A great deal of interest has been generated in the link between the use of antibiotics in food animal feeds and the extent to which the practice contributes to the development of antibiotic resistance. Evidence has continued to accumulate suggesting a relationship between the use of antibiotics in animal feed as a growth promoter and the development of resistant pathogens, particularly vancomycin-resistant enterococci (VRE) (34). Antibiotics added to animal feed not only reduce the normal intestinal flora that compete with the host for nutrients but they also reduce harmful gut bacteria, which may decrease performance and growth by causing subclinical disease. The class of antimicrobial drugs used and the animal species involved may determine the relative importance of each mechanism (35). Although the quantity of antibiotics used in feed varies, the concentration is often referred to as "subtherapeutic." The resulting concentration in the gastrointestinal tract of the animal is sufficient to inhibit the susceptible bacteria and change the composition of the bacterial gut flora.
In Europe, colonization with VRE appears to occur frequently in persons outside the health care setting. An important factor associated with VRE in the community in Europe has been avoparcin, a glycopeptide antimicrobial drug used for years in many European nations at subtherapeutic doses as a growth promoter in food-producing animals. The use of avoparcin as a growth promoter has created in food animals a major reservoir of Enterococcus faecium, which contains the gene bundle for resistance for vancomycin. E. faecium is of particular concern because it is present in the normal intestinal flora of nearly all warm-blooded animals, including humans. Furthermore, glycopeptide-resistant strains of E. faecium can be transmitted from animals to humans. Two antimicrobial classes expected to provide the future therapeutic options for treatment of infections with VRE have analogs among the growth promoters, and a huge animal reservoir of resistant E. faecium has already been created, posing a new public health problem.
Although there are more food animals than humans, the selective pressure favoring VRE in Europe can be estimated to be much higher in food animals than in humans. More of the glycopeptide antibiotic avoparicin was used for growth in animals in Denmark in 1 yr than the amount of vancomycin that was used in all of Europe and the United States used for treating ill humans in the same time period (36).
Denmark is illustrative of the problem. VRE are frequently present in food produced in Denmark as well as in food imported into Denmark from other European countries (37). Several studies in Europe provide evidence that humans are frequently fecal carriers of VRE (38,39). This suggests that VRE can be ingested from food in Europe. Other data in Europe provide additional compelling evidence. Data from the Netherlands that indicates that VRE was not detected in strict vegetarians, suggesting that the source of VRE is contaminated meat (39).
It has been suggested that antimicrobial agents should not be used for growth promotion in animals if they are used in human therapeutics or are known to select for cross-resistance to antimicrobial drugs used in human medicine (34). Adherence to the World Health Organization recommendations (40) will ensure a systematic approach toward replacing antimicrobial growth promoters with safer nonantimicrobial drug alternatives. The European Community countries entered this process in December 1998 when four growth promoters (tylosin, spiramycin, bacitracin, and virginiamycin) were banned because of their structural relatedness to therapeutic antimicrobial drugs used for humans (41).
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