By Robyn Marshall
Antibiotics transformed human health beyond recognition after World War II. No longer were children and adults dying of common bacterial diseases dreaded by our grandmothers — pneumonia, tuberculosis, polio, scarlet fever, whooping cough, rheumatic fever, etc. But now, after a 50-year golden age in fighting infection, these diseases threaten to return with a vengeance due to the emergence on a grand scale of bacterial resistance to antibiotics.
The problem is not so much doctors' over-prescription of antibiotics to patients, although that hasn't helped. Australians are the greatest users of antibiotics per capita in the world. The problem is the massive worldwide use of antibiotics to enhance production in the livestock industry.
In Australia, about 75% of the 1 million kilograms of antimicrobials used each year are for non-human use. Some 660,000 kilos (or 62%) are used as feed supplements to livestock. Some 132,000 kilos (13%) are used for veterinary medicine, compared to 261,000 kilos for human use, based on 1993 figures.
Antibiotic-supplemented feed is given to chickens, turkeys, pigs, cattle, sheep and fish. There are no details available for Australia, but nearly 80% of chickens, 75% of pigs, 60% of feedlot cattle and 75% of calves marketed in the United States have been fed an antibiotic.
With intense livestock farming, the housing of large numbers of animals in small areas means that disease outbreaks are frequent. Antibiotics are used on a massive scale to control and prevent these outbreaks.
Mobile resistance
Antibiotic resistance in bacteria arises from a chromosomal mutation in a gene that then allows the bacteria to withstand the harmful effect of an antibiotic on its metabolism or rates of cell division. The CSIRO has found that the genes for antibiotic resistance are kept together in a discrete mobile element, called a gene cassette, that can slot into a specific place in the bacterial chromosome, called an integron. It can also jump out of the chromosome to form a small piece of circular DNA known as a plasmid.
The cassette or plasmid can hold together several modified genes which confer resistance to a very large number of antibiotics. The mobility of this plasmid means that bacteria in livestock can transfer their antibiotic resistance to bacteria that infect humans, something previously considered unlikely.
This occurs either when humans eat infected meat, as with salmonella, or through a farm worker who acquires the bacteria in their gut from handling manure. Contaminated hands, water, food equipment and the environment create routes for resistant organisms to move from animals to people.
Once resistant bacteria have multiplied under the influence of antibiotics, they form a reservoir from which resistance can spread. On a larger scale, these reservoirs include the gastrointestinal tract of humans, or animals, water containing resistant bacteria, animal feedlots or hospitals with patients or staff who are carriers.
Antibiotic resistant bacteria have been found in animal sewage, waste lagoons and abattoir effluent, as well as in contaminated surface waters, sea water and soil. They have also been found on beef, chicken, turkey and pig carcases and processed meat products. The national and international transportation of humans and animals also increases the dispersal rates.
Cases
In 1995, two French researchers treated a 16-year-old boy from Madagascar who had the bubonic plague caused by a Yersinia pestis infection. He recovered, but only after the plague bacteria had been treated with eight types of antibiotics, including all those previously used to treat plague such as streptomycin, tetracyclin and streptinomycin. This new strain of the "black death" of the 14th century, which wiped out 75% of the populations of Europe and Asia, was contained this time, but if an outbreak was to occur on a large scale in the future its containment could not be guaranteed.
The resistance rate in Australia to Streptococcus pneumoniae, which causes pneumonia, has risen from zero to 10% in six years. In the US, the resistance rate to Staphylococcus aureus, or golden staph, is about 30%. In Australia it is only 1%, but climbing.
There is now strong evidence that bacterial resistance to the glycopeptide vancomycin, the last drug available to treat golden staph, arose in the animal livestock industry from the unlimited use of another glycopeptide antibiotic called avoparcin. Avoparcin and ardactin (another glycopeptide) have been used since the 1970s on boiler chickens, pigs, turkeys, beef, cattle and lambs throughout Europe, Australia and South America.
The death of a transplant patient in Newcastle a year ago was thought to be due to a vancomycin-resistant bacteria which originated from antibiotic-fed ducks on a Newcastle farm. If vancomycin resistance becomes widespread, there will be nothing hospital staff can do but watch patients die from uncontrolled infection.
A strain of Salmonella newport resistant to ampicillin, carbenicillin and tetracycline which caused an outbreak among consumers in 1985 came from contaminated hamburger meat. Similarly, fluoroquinolone resistance in Campylobacter species in humans was linked to the use of this antibiotic in chickens.
Antibiotic resistance arising from animals will go largely unnoticed unless bacteria is collected from both humans and animals and a full genetic profile is obtained.
Monitoring
In Australia, 58 antibiotics are registered for use in animals. Of these, 18 are accepted for use as feed supplements, eight are registered without a schedule, allowing unrestricted use, and 11 are classified as growth promoters. Antibiotics that are unscheduled include the glycopeptides, similar to vancomycin.
There is no formal surveillance to monitor compliance to scheduling regulations. The only monitoring of antibiotics use in livestock production is the measurement of antibiotic residues in meat, but the common practice of withdrawing the antibiotic a few days before slaughter means antibiotics use in the industry is underestimated.
Research into antibiotics is declining because governments have become dependent on big pharmaceutical companies for new drugs. The cost of developing a new drug is close to $500 million over 10 years, including expensive clinical trials, and a new antibiotic could be compromised before it reached the market.
Bacterial resistance to new antibiotics is developing so fast that pharmaceutical companies are finding it unprofitable to invest in new antibiotics. And until the authorities clean up our food supply and the use of antibiotics in animals is tightly regulated, or better still eliminated, there is probably little long-term advantage in developing new antibiotics at present.
Studies have shown that pigs reared in scrupulously clean barns do not need growth promoters and antibiotics. Procedures such as isolating sick animals to prevent the transmission of diseases and good hygiene in abattoirs could be easily implemented.
The problem is that no capitalist government will even begin to think about enforcing or controlling the use of antibiotics in feedlots because this would put its livestock industry at a great disadvantage in the competition with other countries for markets. So, until there is a disaster of mass proportions or an outbreak in which hundreds of people are infected by food containing bacteria that can't be treated, this problem which threatens human beings very survival will likely remain unaddressed.
[Some information for this article was drawn from Dr Susan Benson's article in Life Science, February 1998.]