Dr Ho Wegener, Denmark

Modern food production involves large-scale use of antimicrobial agents. From a medical point of view, this use may give rise to concern because of the risk of resistance development. Resistant organisms in food may impact on human health, either directly by causing foodborne infections, or indirectly by transferring resistant genes to other medically important bacterial pathogens. In recent years, much attention has been devoted to the use of antibiotics in animal husbandry. However, antimicrobial agents are also used in aquaculture and in plant protection. Our knowledge of the extent of this use, and of its potential public health consequences, is very incomplete.

Modern intensive food animal production involves large-scale use of antimicrobials for control of so-called “production-related” bacterial infections, e.g. infections associated with early weaning, mingling of immunologically naive animals from different sources, and frequent removals. In principle, antimicrobial agents are used for three purposes: therapy of infectious diseases; prevention of infections; and growth promotion. By far the largest amounts of antimicrobials administered to animals are given through feed or water. Oral administration exposes the enteric bacterial flora to the antimicrobial, thus exerting selection pressure on the indigenous bacterial flora as well as the target bacteria. Antimicrobial growth promoters are given in so-called “sub-therapeutic doses” in feed. Such dosing does not imply a lower risk of selection of resistant bacteria.

According to pharmaceutical industry estimates for North America and Europe, nearly 50% (in tonnage) of all antimicrobials sold are used in food animals (including poultry). In 1988, almost 15.5 million pounds of antimicrobial agents were used in farm animals in the USA, with almost go% of the antibiotics used in farm animals and poultry being administered in sub-therapeutic concentrations for disease prevention (70%) and growth promotion (30%). In 1997 in the European Union, the total usage of antimicrobials by humans and animals was 10,493 tonnes of active substance, of which human usage was 52%, animal therapeutic use was 33%, and 15% was used as feed additives for growth promotion. More detailed and accurate data on antimicrobial usage are needed. Ultimately, these data could be used to develop strategies for the containment of antimicrobial resistance.

Most of the classes of antimicrobials used in animal husbandry are also used in human medicine, including compounds from classes that are essential for the treatment of serious life-threatening human infections, e.g. fluoroquinolones, aminoglycosides, third-generation cefalosporins, glycopeptides and streptogramins.

In recent years, increasing scientific evidence has supported the contention that resistance to such drugs of last resort can, through their use in animals, develop bacteria capable of causing life-threatening infections in humans, e.g. Salmonella, Campylobacter and Enterococci. A recent specific example was reported in the USA, where a quantitative risk assessment found that the use of fluoroquinolones in poultry was associated with 5000 treatment failures in cases of human campylobacteriosis in 1998.

Another serious concern involves vancomycin-resistant Enterococcus faecium which causes serious infections in hospital patients with an impaired immune system. Vancomycin is very important for the treatment of enterococcal infections, and in many cases vancomycin is the only drug useful for treatment. The isolation of VRE from animals and food has been associated with the use of another glycopeptide, avoparcin, for growth promotion in animals.

Because of the risk of VRE transmission from animals to humans, avoparcin was banned in 1997 to cover all of the EU. The European Union has prohibited the use of antimicrobials as growth promoters if they belong to classes used in human therapy. Some European countries have terminated the use of all antimicrobials for growth promotion in animals.

Factors contributing to the overuse and misuse of antimicrobials in food animals include:

• use of antimicrobials as a tool to support animal rearing under sub-optimal housing and management conditions;

• use of antimicrobials as a tool to enhance feed conversion (growth promoter use);

• lack of information among prescribers as well as users (i.e. farmers) about the risk of resistance development associated with the imprudent use of antimicrobials;

• prescribers generating a substantial proportion of their income from prescribing and selling of drugs; and

• licensing of antimicrobials for use in food animals, which does not sufficiently include an assessment of the public health risks associated with antimicrobial resistance.

All of these factors should be addressed, in order to establish comprehensive strategies to contain antimicrobial resistance associated with the use of antimicrobials in food animals.