(2002; 166 pages)
Veterinary issues contributing to antimicrobial resistance
Professor Henrik C. Wegener, Danish Zoonosis Centre, Copenhagen, Denmark
Administration of therapeutic doses of antimicrobials to food animals constitutes an essential tool for prevention and control of diseases in modern food-animal production. Antimicrobials are also administered in subtherapeutic doses in feed, with the purpose of promoting growth or increasing feed conversion rates. In many countries, the total amounts of active antimicrobials given to food animals largely exceed the amounts used by humans. Most of the classes of antimicrobials used in humans are also used in animals, including some regarded as very important for the management of serious human infections (fluoroquinolones, third-generation cephalosporins, glycopeptides, streptogramins, etc.). Large amounts of antimicrobials are also used in aquaculture and in plant production. The magnitude and pattern of this use are currently not well known.
The use of antimicrobials in food animals promotes the selection and spread of resistant bacteria, some of which can cause disease in animals or humans. Other bacteria may serve as reservoirs of resistance, which may subsequently be transmitted to pathogenic bacteria of animals or humans.
Some of the genera and species that have been studied in most detail in this context are Salmonella, Campylobacter, Escherichia coli and enterococci. For the Gram-negative enteric bacteria, the emergence of resistance to fluoroquinolones following their licensing and use for food animals has caused concern. Fluoroquinolones are used for standard empirical therapy of severe gastrointestinal tract infections in humans. Recent treatment failures and increased mortality rates associated with fluoroquinolone-resistant salmonella infections have added to this concern. A quantitative risk assessment by the US Food and Drug Administration estimated that each year in the USA more than 10 000 patients experienced a campylobacter infection that did not respond to fluoroquinolone treatment because of fluoroquinolone use in poultry production.
Enterococci are commensal organisms of the animal and human gastrointestinal tracts. They are also opportunistic pathogens, causing severe infection in vulnerable hospital patients. The use of certain antimicrobials, particularly glycopeptides and streptogramins, as growth promoters for food animals has been associated with the emergence and spread of enterococci through the food chain that are resistant to important last-resort antimicrobials for humans.
In 1997, a WHO Expert Consultation on the Medical Impact of the Use of Antimicrobials in Food-producing Animals recognized the seriousness of the situation and recommended that strategies for prudent use of antimicrobials in food animals be developed and implemented to protect public health. In 2000, WHO published The WHO Global Strategy for the Containment of Resistance in Animals Intended for Food. Among the key recommendations were the following:
• Prelicensing evaluation should include considerations of resistance of potential public health significance.
• Prescriptions should be obligatory for all antimicrobials used for disease control.
• National systems to monitor antimicrobial use in food animals should be developed and implemented.
• Systems for monitoring of resistance should be developed and implemented nationally, to support timely corrective action.
• Guidelines should be developed for veterinarians to reduce overuse and misuse of antimicrobials.
• Use of antimicrobial growth promoters should be terminated or rapidly phased out.
In the European Union the use of antimicrobials that confer resistance to antimicrobials used for human therapy has been banned since 1999. The European Commission has furthermore proposed a complete phasing out of all antimicrobial growth promoters before the end of 2006. Some EU countries have already phased out growth promoters completely. This has led to a sharp reduction in the levels of resistant bacteria in animals and food, with little adverse impact on productivity or animal health. Discontinuation of the use of antimicrobials for growth promotion, and reduction of misuse and overuse of therapeutic antimicrobials in food animals, can reduce the total amount of antimicrobials used in food-animal production by at least 50%.