Much media attention has been focused on the use of antibiotics in animals, particularly the animals we eat, and the potential spread of resistance to bacteria which infect humans. Although the problem was recognised over 30 years ago1, few countries acted upon it until recently. In the early 1990s a link was identified between the emergence of vancomycin-resistant Enterococcus faecium with the vanA gene (vanA EF) and the use of avoparcin, a vancomycin analogue, as a growth promoter in pig and poultry production.

Australian antibiotic use in farming, medicine and veterinary medicine is high. During 1992-7 an annual average of 399 tonnes or 56% of all antibiotics by weight was used in stock feed. Humans consumed 251 tonnes or 36%, while 54 tonnes or 8% were used in veterinary therapeutics.2

A very wide range of antibiotics is used for many different reasons in animal husbandry, agriculture, and in veterinary practice. Common sense and a knowledge of bacterial genetics tell us that we need to monitor the emergence of resistance and only give antibiotics to animals when it is therapeutically rational and cost-effective to do so. Resistant bacteria can be generated in animals, transferred to humans and amplified to become a major human problem. These bacteria may either cause disease in humans or transfer their resistance genes to normal flora that may later become pathogenic. Good food hygiene will slow the transfer rate but will not eliminate the transfer of resistance. Antibiotics should therefore be given to animals only when necessary and for the shortest effective duration.

While short courses at therapeutic doses minimise resistance selection, a significant proportion of the antibiotics used in animals are given in feed at low doses over many weeks of the production cycle. Antibiotics are used in this way by the so-called intensive animal industries, especially meat poultry and pig production, where the animals are housed in close quarters in large numbers (just like hospitals!). Cross-infection is a problem, and antibiotics play an important role in suppressing infection and controlling stock loss, as well as in promoting the animals' growth.

These patterns of use generate maximum selective pressure for antibiotic resistance. This would not be a problem if the antibiotics used were from different classes and had a different mechanism of action from those used in humans. Unfortunately, a number of drugs used in this way belong to the same classes and select for cross-resistance to human antibiotics. Examples include avoparcin (a glycopeptide), virginiamycin (a streptogramin which selects for cross-resistance to the newly released drug quinupristin/dalfopristin) and certain macrolides.

Before calling for blanket decisions to prohibit all antibiotic use in animals, we need to understand the data suggesting that resistance has been transferred from animals to humans via the food chain. The data concerning resistance transfer are limited to a small number of organisms and antibiotics such as vanA EF and avoparcin, thermophilic Campylobacter species and fluoroquinolones, multi-drug resistant Salmonella species and aminoglycoside resistance in E. coli. Apart from these examples there is little information to show just how much resistance in human bacteria can be traced back to the use of antibiotics in animals.

Data in Australia are even more limited. For instance, although avoparcin has been widely used in Australia since the mid 1980s, and vancomycin-resistant enterococci (VRE) emerged in human isolates in Australia in 1994, the predominant type of VRE contain a different gene from that attributed to avoparcin use. One small study of animal samples in the Hunter Valley revealed only two strains of VRE, and their association with avoparcin use remains unclear.3

The concern for human medicine is that avoparcin and virginiamycin select for resistance to drugs that are reserved for infections caused by bacteria resistant to multiple other antibiotics (`last-line' drugs). After sustained pressure about this issue the European Union decided to suspend the use of avoparcin as an in-feed antibiotic. Subsequently it was withdrawn from the international market, including Australia. The Europeans have also suspended other in-feed drugs, including virginiamycin, tylosin, spiramycin and bacitracin.

What could or should be done about antibiotic use in animals? Australia has produced a blueprint for tackling this problem.2 A number of recommendations have been made in the areas of regulation, surveillance and monitoring, infection prevention, education and research. One key recommendation is that of phasing out the long-term, low dose use of antibiotics that can generate resistance to 'last-line' human antibiotics.

The most important feature of the recommendations is that rational antibiotic use is the responsibility of all prescribers and users, medical practitioners and veterinarians, patients and farmers. Antibiotic use of any type and the antibiotic resistance it generates is a public health issue. The use of antibiotics in animals may be making a lesser contribution than inappropriate prescribing to resistance problems in humans. However, all users must endeavour to minimise resistance for the sake of healthy animals, food and humans.

E-mail: [email protected]

 

John Turnidge

Professor, Microbiology and Infectious Diseases Department, Women's and Children's Hospital, Adelaide