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Antibiotic Resistance

Antibiotics in agriculture

Very large quantities of antibiotics are fed to animals, especially in the intensive industries of pigs, meat chickens and feedlot cattle. Some antibiotics are used to treat diseases in animals, in the same way they are used to treat human diseases. But much larger quantities are mixed into the animals’ feed on a regular basis, mainly to increase their growth rate. The antibiotics are thought to have this effect by killing bacteria that could use some of the food in the animal's gut, by increasing absorption of nutrients through the gut lining, and in feedlot cattle by aiding the digestion of grain.

There is now a very real danger that this abuse of antibiotics is producing antibiotic resistant bacteria that can cause disease in humans and animals. These diseases will be increasingly difficult to treat because of the antibiotic resistance.

There have been a number of conferences and reports on this subject, because it is becoming a cause for international concern. In 1997 there was a World Health Organization workshop. In 1999 the Australian Joint Expert Advisory Committee on Antibiotic Resistance (JETACAR) submitted its report to the Commonwealth Ministers for Health and for Agriculture. Unless otherwise indicated, information in this document comes from the JETACAR report (1). The report is available online .

Antibiotic use in Australia

In the 1990s there were around 700 tonnes of antibiotics imported into Australia each year. These drugs were used as follows:

• 35.7% human medicine

• 7.6% veterinary medicine (eg mastitis in dairy cows, pneumonia in pigs)

• 56.6% mixed into stockfeed

In the intensive animal industries low doses of antibiotics are mixed into the feed over a long period of time. The two main aims of using drugs in this way are to prevent commonly occurring diseases and to increase the growth rate of animals. The main diseases are as follows:

• bloat and acidosis in feedlot cattle, which is excessive acid and gas in the digestive system resulting from an unnatural grain diet;

• proliferative enteritis in pigs, an intestinal infection which is largely a disease of intensive farming;

• necrotic enteritis in meat chickens, which is also an intestinal infection.

If animals were not kept in unnatural and crowded conditions, and expected to show an abnormally high growth rate, the use of these large quantities of antibiotics would not be necessary.

The following antibiotics are registered for use in food animals in Australia:

Antibiotic family	Antibiotic	Animals
Arsenicals	3-nitro-arsonic-acid	Pigs, Poultry
Glycopeptides	Avoparcin	Pigs, Poultry, Cattle
Macrolides	Kitasamycin	Pigs
	Oleandomycin	Cattle
	Tylosin	Pigs
Polyethers	Lasolocid	Cattle
(ionophors)	Monensin	Cattle
	Narasin	Cattle
	Salinomycin	Pigs, Cattle
Polypeptides	Bacitracin	Poultry
Quinoxolines	Olaquindox	Pigs
Streptogramins	Virginiamycin	Pigs, Poultry
Others	Flavophospholipol	Pigs, Poultry, Cattle

These drugs are very readily available, without veterinary consultation, as JETACAR has pointed out:
" In Australia, provided that antibiotics are registered for growth promotant uses, (including avoparcin and virginiamycin), they are available for over-the-counter sale to livestock owners, feed-millers and feed mixers. '

The use of antibiotics is reflected in the numbers of antibiotic resistant bacteria found in animals. In Salmonella bacteria isolated from animals in Australia between 1989 and 1994, the following percentages were resistant to one or more antibiotics:

• Pigs - 55%

• Poultry - 41%

• Cattle - 13%

• Sheep - 6%

Antibiotics are used much less frequently in the extensive sheep and cattle grazing industries, and this fact is reflected in the lower percentages of antibiotic resistant bacteria in these animals compared to intensively farmed pigs and chickens.

Development of antibiotic resistance

Individual bacteria differ in their susceptibility to antibiotics - even when most are killed by a particular antibiotic, a few may carry a gene that allows them to survive and reproduce. As the antibiotic continues to be used, the resistance bacteria will make up a larger and larger percentage of the population because the susceptible bacteria keep dying and the resistant ones keep reproducing.

Antibiotic resistance isn't only passed on from parent to offspring, it can also be passed from one bacterial cell to another when they come into contact.

Unlike mammals, bacteria only have one chromosome, a long string of genetic material coiled in the centre of the cell. However, they also have one or more small rings of genetic material called plasmids in the body of the cell.

A plasmid from one bacterial cell can move into another cell with which it has physical contact. Such transfers occur most frequently between bacteria of the same strain and species, although cross-species transfers can occur.

When a plasmid carrying an antibiotic resistance gene moves from one cell to another, the recipient cell now has the resistance whereas previously it may have been susceptible to antibiotics.

A particular gene may give resistance to more than one antibiotic. For example, bacteria in humans have acquired resistance to the antibiotic vancomycin used in human medicine from bacteria which acquired resistance to avoparcin used as a growth promotant in animals.

A plasmid may also carry more than one resistance gene, giving the recipient cell resistance to several antibiotics at the same time. Plasmids carrying 5 or more resistance genes are commonly found in antibiotic resistance pathogens.

The consequences of such multi-gene plasmid transfers are particularly worrying, as JETACAR points out:
" ...if an antibiotic from an antibiotic family that is not used in human medicine is used in animal production, it may still affect the levels of bacteria that are resistant to important human antibiotics ".

Human disease

Antibiotic resistance developed in animal industries has so far been mainly a problem for human diseases of the digestive system. This is probably because infection occurs through food, such as meat.

There are 2 ways that antibiotic resistant bacteria from animals can cause disease in humans:

1. the disease-causing bacteria (pathogens) are transferred directly from animals or animal products to humans;

2. the bacteria that are transferred from animals to humans do not themselves cause disease, but transfer resistance genes to human pathogens.

As the JETACAR report states:
" ...there is evidence for direct spread of resistant bacteria form animals to people and subsequent clinical disease. Based on molecular evidence for some species, there is also evidence for the transfer of antibiotic-resistance genes from animal bacteria to human pathogenic bacteria ".

Examples include:

• vancomycin-resistant enterococci (VRE) , developed as a result of using avoparcin, another member of the glycopeptide antibiotic family, in animals. Over 70 strains of VRE have been isolated in Australia.

  There are high rates of resistance to avoparcin in enterococci isolated from pigs and chickens fed this antibiotic. Danish researchers have shown that there is a particular gene sequence for resistance in enterococci from chickens, and an other in enterococci from pigs. Both gene sequences are found in human vancomycin-resistant enterococci (VRE), suggesting that humans acquired these VRE from the animals.

  Dutch researchers found vancomycin-resistant enterococci in 50% of turkey faecal samples, 39% of turkey farmer samples, 20% of samples from people slaughtering turkeys, and 14% of samples from people living near turkey farms. These results show that VRE is more common the more people have contact with turkeys. The study also found that in turkey flocks not fed avoparcin, the prevalence of VRE was only 8%, compared to 60% in flocks fed avoparcin, showing the link between avoparcin and vancomycin-resistance (2).

  Resistance to antibiotics from the glycopeptide family causes medical problems for some people:
  " Enterococcal infections cause problems for hospitalised patients with impaired immune systems and can be treated with glycopeptide antibiotics. Resistance to glycopeptides ... now contributes to increased morbidity and mortality in these patients, as therapeutic alternatives are limited ". (3)

  One alternative in these cases is to use antibiotics from the streptogramin family, however resistance to these drugs is also developing because of the use of virginiamycin in animal feeds.

• fluoroquinolone-resistant campylobacters . There is a high degree of relatedness between human and animal isolates of such bacteria, strongly suggesting a link to the use of fluoroquinolones in animal feed. Fluoroquinolones are not registered for use in animals in Australia.

• multi-resistant Salmonella typhimurium DT104 , which is resistant to ampicillin, chloramphenicol, streptomycin, sulfonamides and tetracycline. This pathogen has not yet been found in Australia, but is becoming more common in Europe and the US, and has become a major cause of human gastro-intestinal illness. In the US, multi-drug resistant Salmonella increased from 0.6% of all samples analysed in 1979/80 to 34% in 1996, leading researchers to conclude:
  " The emergence of antimicrobial drug resistance in Salmonella isolates is associated with the therapeutic and nontherapeutic use of antimicrobial agents in food animals ". (4)

The fact that some well-known antibiotic resistant pathogens have not yet been found in Australia is only a small consolation. Firstly, there are many other antibiotic resistant bacteria already existing in Australia. For example an unpublished study of bacteria isolated from pigs in South Australia, and cited by JETACAR, showed enterococci, Salmonella, E.coli and campylobacter resistant to a wide range of antibiotics. Secondly, antibiotic resistance can easily become a world-wide problem because of increased international travel and trade.

The US allows penicillin to be used in food animals, Russia allows the use of chloramphenicol, and the use of antibiotics in shrimp farming in South East Asia is unregulated. Antibiotic resistance which develops as a result can be exported all over the world, as one researchers points out:
" The problems caused by inappropriate use of antibiotics reach beyond the country of origin. Meat products are traded world-wide, and evolving bacterial populations do not respect geographical boundaries ". (3)

Preventing future therapeutic problems

In 1986 Sweden banned the use of antibiotics as growth promotants. In 1995 Denmark, and in 1996 Germany, banned the use of avoparcin because it leads to vancomycin-resistance. Denmark also banned the use of virginiamycin because it can lead to resistance to 2 new and important antibiotics in human medicine. The European Union has suspended use of avoparcin, virginiamycin, tylosin, spiramycin and bacitracin, most of which are still used in Australia.

JETACAR recommended a review of the use of avoparcin, virginiamycin, tylosin, kitasamycin and oleandomycin in Australia because their use could produce resistance to antibiotics used in human medicine. JETACAR also recommended that non-antibiotic methods should be used to increase productivity and prevent disease, and that all antibiotics should be classed as Schedule 4 drugs, available on prescription only.

A World Health Organisation Workshop in 1997 warned in its press release:
" Excessive use of antimicrobials, especially as growth promoters in animals destined for human consumption, presents a growing risk to health and should be reduced... ".

In line with this warning, one member of JETACAR concluded:
" The availability of antibiotics for therapeutic use in animals must not be compromised, but use of antibiotics as growth promotants and for preventative treatment should be phased out in favour of improved hygiene, better management techniques and vaccines ".

As an example, proliferative enteritis and pneumonia, two diseases that are common in intensive piggeries and for which antibiotics are used, are very uncommon when growing pigs are housed in Ecoshelter units rather than in crowded and poorly ventilated sheds. Disease can be prevented through better husbandry. As to increased growth rate, there is no excuse for jeopardising future treatment of human and animal diseases through the use of antibiotics to maximise production and profits. The Swedish example shows that disease can be managed with much less antibiotics than currently used, and that productivity can be quite adequate without antibiotics as growth promotants.

Australia should follow the example of Sweden and ban the use of antibiotics as growth promotants.

References