antimicrobial chemotherapy and use in agriculture was cited in the report from a Rockefeller University workshop on antibiotic resistance as a threat to human health because of the increased propensity for this practice to set up conditions favorable to the selection of resistant bacteria (Tomasz 1994). In that report, however, the conclusion regarding agricultural use of antibiotics as a threat to human health was derived from a single previous review of the issue (Dupont and Steele 1987). The report failed to critically assess data that would take the conclusion to the next logical step—a substantive review of the actual development of disease (incidence, severity) directly related to antibiotic resistance in bacteria of food animals, and not to the mere potential for this to occur.

Threlfall (1992) reviewed the issue of drug resistance and antibiotic use with regard to selection of food-borne pathogens. He concluded that the prophylactic and therapeutic use of such antibiotics contributed substantially to the emergence of multidrug-resistant strains. He cited many examples of the emergence of such organisms from poultry, dairy calves, and pigs that he believed resulted in human disease. Conversely, Shah et al. (1993) reviewed the major pathogens involved in antibiotic-resistant human infections and their resistance patterns, compared them with the organisms and resistance patterns isolated from animals, and concluded that the veterinary pool has not contributed substantially to the overall profile of clinically significant antibiotic-resistant infection in humans. Wiedmann (1993) summarized the monitoring and origin of resistant organisms in humans and suggested that development of resistance could not be generalized but had to be discussed on the basis of specific drugs, bacterial species, or locations. Although he stated that the use of antibiotics in food-animal production had minimal consequences for the treatment of human infections in hospitals, those conclusions must be viewed from the perspective that the effects were minimal because there were alternative antibiotics that could be used to treat the infections.

All of these studies reached valid conclusions based on the interpretation of their data; however, none fully accounted for the issues of interconnectivity between species, genera of bacteria, or human and animal ecosystems. There are studies that critically examine the extent or mechanisms by which microbes pass from animal to human populations. Some microorganism transfers between animals and humans are clinically significant and result in invasive infections. There is no doubt that the passage of antibiotic-resistant bacteria from animals to humans occurs and that it can result from direct contact with animals or their manure (as might occur with workers on the farm [Holmberg et al. 1984b; Bates et al. 1994; Haapapuro et al. 1997]), through indirect exposure to food contaminated with animal-derived bacteria (Witte and Klare 1995), or from person-to-person contact after a primary exposure of nonfarm persons (Lyons et al. 1980). The passage of microorganisms from animals to humans probably also occurs without clinically overt disease in humans or animals, or more frequently, with self-limiting disease that is untreated. Clinically relevant diseases also can be

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