The use of antimicrobials outside human medicine: information from the World Health Organization on the health consequences. (Technical Briefs).

Introduction

There has been an alarming emergence in humans of bacteria with resistance to antimicrobials. Most of the problem is due to the overuse and misuse of antimicrobials by health personnel and patients. Following their 20th-century triumph in human medicine, however, antimicrobials have been used increasingly to treat bacterial disease in animals, fish, and plants. In addition, they have become an important element of animal husbandry (particularly in pig and poultry production) because they have been observed to have growth-enhancing effects at subtherapeutic doses. Antimicrobials also are used in industry--for instance, to eliminate bacterial growth inside oil pipelines.

Scale of Use Outside Human Medicine

* It is estimated that about half of the total amount of antimicrobials produced globally is used in food animals.

* A recent review in Europe has shown that on average, 100 milligrams of antimicrobials are used in animals to produce 1 kilogram of meat for human consumption.

* The increase in meat production in many developing countries is mainly due to intensified farming, which is often coupled with increased use of antimicrobials both for disease therapy and for growth promotion.

Factors Contributing to Overuse of Antimicrobials in Food Animals

* Education on antimicrobial resistance and prudent antimicrobial use is lacking among dispensers and prescribers. One study reported that in 1987, more than 90 percent of all veterinary drugs used in U.S. animals were administered without professional veterinary consultation. Inappropriate doses and combinations are frequent. Furthermore, when antimicrobials are administered to flocks and herds in feed, the result is inaccurate dosing and the inevitable treatment of all animals irrespective of health status.

* Empiric treatment (based on clinical investigations rather than isolation and typing of the causative pathogen) predominates because of the widespread lack of diagnostic services, particularly in developing countries.

* In many countries, including several developed countries, antimicrobials are available over-the-counter. Antimicrobial growth promoters are not considered as drugs and are licensed, if at all, as feed additives.

* Inefficient regulatory mechanisms or poor enforcement of regulations, with lack of quality assurance and marketing of substandard drugs, are important contributing factors. Discrepancies between regulatory requirements and prescribing/dispensing realities are often wider in veterinary medicine than in human medicine.

* Pharmaceutical-industry marketing of antimicrobials influences the prescribing behavior and patterns of use among veterinarians and farmers. Unlike in human medicine, few countries currently have industry codes or government rules for nonhuman use of antimicrobials.

Antimicrobial Use in Aquaculture 

* Various antimicrobials are used in fish and shrimp production, particularly in Asia. Unfortunately, little information is available on the type and amount of antimicrobials used.

* There is an urgent need to review patterns of antimicrobial use in aquaculture. (This need also applies in other areas of antimicrobial use, including plant protection and industry.)

* Some countries have been looking for non-antimicrobial alternatives. Norway has been able to diminish antimicrobial use in aquaculture by more than 90 percent by changing production practices and increasing the use of vaccines.

Consequences--Some Examples

* Studies in several countries have demonstrated an association between use of antimicrobials in food animals and antimicrobial resistance. Some of the antimicrobial-resistant bacteria newly emerging in animals can be transmitted to humans, mainly via meat and other foods of animal origin, or through direct contact with farm animals.

* Soon after the licensing of fluoroquinolones for use in poultry, isolation of fluoroquinolone-resistant Salmonella and Campylabacter in animals--and then in humans--became more common. Community and family outbreaks of salmonellosis and campylobacteriosis resistant to fluoroquinolones have since been reported from several countries.

* Vancomycin-resistant strains of Enterococcus bacteria have emerged in many hospitals around the world. The question has been raised whether vancomycin use in agriculture could have compounded the problem. Indeed, vancomycin-resistant enterococci have been isolated in animals, food, and untreated volunteers in countries where vancomycin is also used as a growth promoter in animals.

* Denmark banned use of vancomycin as an animal growth promoter in 1995, and all European countries followed suit in 1997. After the ban was in place, the prevalence of resistant Enterococcus in animals and food, particularly in poultry meat, fell sharply

* Further study is required to investigate other possible ways antimicrobial-resistant bacteria may be transmitted to humans. One unknown, for example, is the impact on human health of nonmetabolized antimicrobials that are widely distributed into the environment through manure and other effluents from farm animals.

Containment of Antimicrobial Resistance

* Containment will require national and local efforts to reduce use of antimicrobials. Few countries have active surveillance for antimicrobial resistance of bacteria in food animals and food of animal origin. Existing programs rarely involve all relevant zoonotic and commensal microorganisms and do not test for all the antimicrobials that maybe relevant from a public-health perspective.

* The World Health Organization (WHO) is developing a Global Strategy for the Containment of Antimicrobial Resistance and is working with national agencies and institutes on the problem.

* Through legislation, some countries have taken steps to reduce the problem. In 1997, the European Union banned all antimicrobial animal growth promoters also used in human medicine, In 1986, Sweden banned the use of all animal growth promoters, even those not used in human medicine. Denmark voluntarily suspended the use of animal growth promoters in 1999, and Switzerland did so in 2000. Studies in Denmark have shown that the voluntary suspension resulted in an overall reduction of antimicrobial use in Danish livestock of more than 60 percent with no significant economic impact or negative change in animal health status or food safety.

Further Information

* The Global Salm-Surv is a Web-based network of individuals and laboratories working on isolation, identification, and antimicrobial-resistance testing of Salmonella and surveillance of salmonellosis. It can be found at <http://www.who.int/salmsurv>.

* WHO's global principles for antimicrobial use in agriculture can be consulted at <http://lwww.who.int/emc/diseases/zoo/who_global_principles.html>.

* Readers also may be interested in WHO fact sheets Number 255, on Campylobacter and Number 139, on multi-drug-resistant Salmonella -typhimurium. Both can be obtained, along with all WHO press releases, at <http://www.who.int>.

* This article was adapted from WHO Fact Sheet Number 268.