14.1 This thesis is based on a number of monitoring and research programmes initiated at the Danish Veterinary Laboratory with the aim to determine the occurrence, selection and spread of resistance to antimicrobial agents used for growth promotion. The thesis gives a brief overview of the use, consumption, function and benefit of antimicrobial growth promoters and a more thorough description of the potential resistance problems arising by the use of these agents. 14.2 THE USE OF ANTIMICROBIAL AGENTS IN A HISTORICAL PERSPECTIVE: Soon after the introduction of antimicrobial agents for therapy of bacterial infections in humans and animals, the growth promoting effect of antimicrobial agents was observed, and since the beginning of the 1950'ties antimicrobial agents have been included in feed for food animals as a way to improve growth and reduce production costs. 14.3 CONSUMPTION OF ANTIMICROBIAL GROWTH PROMOTERS: Exact figures on the consumption of antimicrobial agents for clinical and growth promoting purposes are very difficult to get, and estimates are only available for a few countries. In Denmark, the total annual consumption of antimicrobial agents for growth promotion increased from 67 tonnes to 116 tonnes from 1989 to 1995. After the ban on avoparcin in 1995 the total consumption of growth promoters decreased to 94 tonnes. An increase up to 107 tonnes took place during 1996 and 1997, but during 1998, the consumption decreased to approximately 49 tonnes. The data that are available for different countries show that the use of antimicrobial agents for growth promotion normally equals or exceeds the usage of antimicrobial agents for therapy for food animals. Based on the information available, it can be estimated that the financial sale of antimicrobial agents for animals amounts to approximately 25% to 35% of the world-wide sale, of which the use of antimicrobial agents as feed additives is at least 50%. 14.4 MODE OF ACTION OF ANTIMICROBIAL GROWTH PROMOTERS: The mode of action of antimicrobial growth promoters is not fully understood. However, the main effects are believed to be a reduction of the growth of bacteria in the intestinal tract and thereby less microbial degradation of useful nutritients, and the prevention of infections with pathogenic bacteria. 14.5 BENEFIT FROM THE USE OF ANTIMICROBIAL GROWTH PROMOTERS: Numerous studies on the economic benefit of the use of antimicrobial growth promoters have been performed. The growth response is normally larger in young animals than in older animals. Large variations in the estimates have been observed, but in general a improvement in growth rate and feed utilisation has been observed. 14.6 SUSCEPTIBILITY AND RESISTANCE TO ANTIMICROBIAL GROWTH PROMOTERS: The definition of a bacterium as susceptible or resistant to an antimicrobial agent ultimately depends on clinical outcome. Since the exact mode of action of antimicrobial growth promoters are not known, the only way to define break points is based on the population distributions of susceptibilities to different agents. For antimicrobial agents used both for therapy and growth promotion the break points for therapy have been used. For avilamycin, avoparcin, flavomycin, monensin and salinomycin, that are used for growth promotion only, tentative break points based on population distributions have to be defined. The tentative break points for avoparcin and avilamycin have been confirmed by cross-resistance to other antimicrobial agents belonging to the same class and the presence of resistance mechanisms. 14.7 OCCURRENCE OF AND SELECTION FOR RESISTANCE TO ANTIMICROBIAL AGENTS USED FOR GROWTH PROMOTION: Information on the occurrence of resistance is needed to guide policy and detect changes that require intervention strategies. In 1995, a continuous monitoring of antimicrobial resistance in bacteria isolated from food animals was established in Denmark. Among food animals three categories of bacteria (indicator bacteria, zoonotic bacteria and animal pathogens) are continuously isolated from broilers, cattle and pigs and tested for susceptibility to antimicrobial agents used for therapy and growth promotion by disc diffusion or MIC-determinations. In all known cases antimicrobial resistance has emerged following the introduction of new antimicrobial compounds for therapy. The occurrence of resistance to antimicrobial agents used for growth promotion indicates that resistance will also emerge following the introduction of antimicrobials for growth promotion. Comparison of the occurrence of resistance among reservoirs with different usage of antimicrobial agents for growth promotion also shows that the occurrence of resistance will follow the usage. (ABSTRACT TRUNCATED)