Evidence supports ban on growth promotion use of antibiotics in farming
David Cohen, M.D.·Published 17 November 2011·10 min read
Key points
In a review study, researchers from Tufts University School of Medicine zero in on the controversial, non-therapeutic use of antibiotics in food animals and fish farming as a cause of antibiotic resistance.
According to estimates, antibiotics are eight times more likely to be used for non-therapeutic purposes than for treating a sick animal.
- The long-term administration of antibiotics in animal feed creates an optimal environment for antibiotic resistance genes to multiply.
Antibiotic resistance is the ability of a microorganism to withstand the effects of an antibiotic.
In a review study, researchers from Tufts University School of Medicine zero in on the controversial, non-therapeutic use of antibiotics in food animals and fish farming as a cause of antibiotic resistance. They report that the preponderance of evidence argues for stricter regulation of the practice. Stuart Levy, a world-renowned expert in antibiotic resistance, notes that a guiding tenet of public health, the precautionary principle, requires that steps be taken to avoid harm.
"The United States lags behind its European counterparts in establishing a ban on the use of antibiotics for growth promotion. For years it was believed that giving low-dose antibiotics via feed to promote growth in cows, swine, chickens and the use of antibiotics in fish farming had no negative consequences. Today, there is overwhelming evidence that non-therapeutic use of antibiotics contributes to antibiotic resistance, even if we do not understand all the mechanisms in the genetic transmission chain," says Levy, MD, professor of molecular biology and microbiology and director of the Center for Adaptation Genetics and Drug Resistance at Tufts University School of Medicine.
For the past 70 years, humans have relied on antibiotics to combat bacterial infections such as streptococcus, meningitis, tuberculosis and urinary tract infections. The misuse and overuse of antibiotics, however, has contributed to antibiotic resistance, making antibiotics less effective at saving lives. Levy and co-author Bonnie Marshall summarize and synthesize the findings of a large number of studies assessing the link between antibiotic resistance and the use of non-therapeutic antibiotics in livestock and fish farming. Highlights include the following.
The use of non-therapeutic antibiotics is widespread
According to estimates, antibiotics are eight times more likely to be used for non-therapeutic purposes than for treating a sick animal.
Current practices set the stage for the rapid spread of antibiotic-resistant bacteria
- The long-term administration of antibiotics in animal feed creates an optimal environment for antibiotic resistance genes to multiply. Essentially, treated animals become "factories" for the production and distribution of antibiotic-resistant bacteria such as Salmonella and Methicillin-resistant Staphylococcus aureus (MRSA), a troubling infection that is resistant to common antibiotics.
- Bacteria can transfer antibiotic resistance to other bacteria, and multiple different resistance genes can be linked together in this process. Thus, even if farmers turn to antibiotics that are not commonly used to treat people, these drugs – given over long periods of time – can also promote resistance. Several studies demonstrated that antibiotic-resistant bacteria can easily spread from animals to people in close contact with animals, such as veterinarians, slaughterhouse workers, farmers, and the families of farmers.
Written and revised by
David Cohen, M.D.
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- As much as 90 percent of antibiotics given to livestock are excreted into the environment. Resistance spreads directly by contact and indirectly through the food chain, water, air, and manured and sludge-fertilized soils.
- The broad use of antibiotics in fish food in farm fishing, particularly overseas, leads to leaching where it can be washed to other sites, exposing wild fish to trace amounts of antibiotics.
Antibiotic resistance
Antibiotic resistance is the ability of a microorganism to withstand the effects of an antibiotic.
It is a specific type of drug resistance. Antibiotic resistance evolves naturally via natural selection through random mutation, but it could also be engineered by applying an evolutionary stress on a population.
Once such a gene is generated, bacteria can then transfer the genetic information in a horizontal fashion (between individuals) by plasmid exchange.
If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug. Causes Antibiotic resistance can also be introduced artificially into a microorganism through transformation protocols.
This can be a useful way of implanting artificial genes into the microorganism. Antibiotic resistance is a consequence of evolution via natural selection.
The antibiotic action is an environmental pressure; those bacteria which have a mutation allowing them to survive will live on to reproduce.
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The consequences of antibiotic resistance are great
According to the Centers for Disease Control and Prevention, antibiotic-resistant infections cause longer and more expensive hospital stays, and greater risk of death. Each year in the US antibiotic-resistant infections result in $20 billion in additional health care costs and $8 million in costs in additional hospital days. If antibiotics are ineffective, patients may end up paying more in search of alternative drugs, and enduring a wider range of side effects.
Bans on the use of non-therapeutic antibiotics are effective in diminishing antibiotic resistance - Bans in several European countries have led to decreases in antibiotic resistance. Bans in Denmark and Germany have not only decreased the presence of antibiotic-resistant bacteria in farm animals, they have decreased the presence of these bacteria in humans.
- Alternative farming practices such as reducing animal crowding, improving hygiene, and improving use of vaccines have been shown to compensate for some of the growth benefits conferred by non-therapeutic antibiotics.
Levy and Marshall also highlight areas of study that may improve our understanding of the link between antibiotic use in animals and the spread of antibiotic-resistant bacteria. Modern genetic techniques are helping, they report, but there are still gaps in our understanding at each stage of the transmission chain.
Why should I worry about antibiotic resistance? If you take antibiotics that cannot fight the bacteria they are supposed to kill, your infection can last longer. Instead of getting better, your infection might get worse. You might have to make several visits to your doctor's office. You might have to take different medicines or go to a hospital to get stronger antibiotics given intravenously (through an IV needle into your vein).
At the same time, your family members or other people you come into contact with will be exposed to the resistant bacteria you have. Then these people might also develop infections that are hard to treat.
Every time you take antibiotics when you don't need them or you do not take all of the antibiotics recommended by your doctor, you increase the chance that you will someday get an illness that is caused by resistant bacteria.
"Aquaculture, or fish farming, has been relatively understudied, yet water is a prime medium for the spread of antibiotic-resistant bacteria," says first author Bonnie Marshall, MA, MT (medical technology), senior research associate in the Levy laboratory at Tufts University School of Medicine.
"While the use of non-therapeutic antibiotics remains contentious, the evidence is strong enough to merit precaution. Antibiotics save lives. When infections become resistant to primary antibiotics, and alternative antibiotics must be used, health care costs increase. As more infections become more resistant to more antibiotics, we run the risk of losing more of our arsenal of antibiotics, resulting in needless deaths. It's important to consider what we stand to gain versus what we stand to lose," concludes Levy.
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The Food & Drug Administration (FDA) has already taken some steps toward stricter regulation of non-therapeutic antibiotic use, acknowledging that the practice is in conflict with protecting the public health and proposing measures to limit the use of these drugs in animals. Levy and his colleagues in the field of infectious disease have called for antibiotics to be classified by the FDA as "societal drugs," establishing specific regulations to protect the efficacy of the drugs.
Levy is president of the international Alliance for the Prudent Use of Antibiotics, and is a fellow of the American College of Physicians, the Infectious Disease Society of America, the American Academy of Microbiology and the Association for the Advancement of Science. He has published more than 300 papers, edited four books and two special journal editions devoted to antibiotic use and resistance, and is author of The Antibiotic Paradox: How Miracle Drugs Are Destroying the Miracle. He is also co-founder and chief scientific officer of Paratek Pharmaceuticals, Inc. Dr. Levy received the 2011 Hamao Umezawa Memorial Award from the International Society of Chemotherapy, given in recognition of his lifetime contributions in the field of antibiotic resistance.
What happened to antibiotics? Once considered the universal answer to infectious disease, we now know the effective life span of these once-miraculous drugs is limited. The problem, simply, is that we "got complacent," says Barry Kreiswirth of the Public Health Research Institute, who makes a living analyzing strains of tuberculosis that resist as many as nine antibiotics.
It's not just TB. "The global increase in resistance to antimicrobial drugs, including the emergence of bacterial strains that are resistant to all available antibacterial agents, has created a public health problem of potentially crisis proportions." That's the word from the American Medical Association (AMA), which studied the issue in 1995, and seldom fulminates in such alarmist terms.
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The experts are sounding the alarm about antibiotic resistance because of grim new evidence:
Resistance happens quickly, in parallel with the use of antibiotics. An 11-year study of cancer patients at a hospital in Switzerland (see the 4/28/94 New England Journal of Medicine) found that no strains of Escherichia coli (a common intestinal bacteria that can be pathogenic) resisted any of the fluoroquinolone antibiotics between 1983 and 1990. But between 1991 and 1993, 28 percent of the strains tested were resistant to all five of them. During the study period, the percentage of patients getting antibiotics rose from 1.4 percent to 45 percent.
(Updated 1 May, 1998: Under a new National Institutes of Health grant, scientists have begun examining whether harmless bacteria carry resistance genes and transmit them to pathogens. Already, it's thought that the bacterium Haemophilus influenzae, which causes ear infections, gained resistance to the antibiotic ampicillin during a gene transfer from Escherichia coli, during the 1970s. Why would a harmless bacterium acquire such resistance? Because any organism exposed to antibiotics faces the same selective pressure that causes pathogens to become antibiotic resistant. One leader of the new research group, University of Illinois at Urbana-Champaign microbiologist Abigail Salyers, said resistance can lurk undetected in harmless organisms. She called the presence of resistance in pathogens "the tip of the iceberg compared to what's out there in the environment." See "New Hunt for the Roots of Resistance," Science, 3 April 1998, p. 27. End update.)
It's widespread. In Atlanta, a 1994 study of infections caused by Streptococcus pneumonia found that 25 percent of 431 patients had a bug that resisted penicillin, and that 25 percent of all cases were resistant to several antibiotics.
It spreads fast: thanks in part to jet planes. Resistant tuberculosis has spread from New York City to Denver, Florida, Nevada and Paris.
Bacteria learn from our mistakes: Once resistance develops, all offspring of that bacterium get it. "Once the resistant strain is made, everybody who is infected with it will have that resistance problem," says Kreiswirth. And because these organisms then pick up further resistance to other drugs, he says, "All it's going to do is get worse." You can skip ahead to our coverage of the mechanisms of resistance.
Hospitals serve as centers for the formation and transmission of drug-resistant organisms. About 2 million Americans are infected in hospitals each year and more than half of these infections resist at least one antibiotic, according to Dennis Maki, a University of Wisconsin-Madison expert in hospital infections. In 1992, 13,300 hospital patients were killed by drug-resistant bacteria in the United States.
Resistance is an especially vexing problem for people with impaired immune systems, such as AIDS, and cancer patients, and recipients of organ transplants. About 90 percent of AIDS patients who get multiple-drug resistant TB die.
Bonnie Marshall was supported in part by The Pew Charitable Trusts. Stuart Levy is a consultant to the Pew Charitable Trusts.
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Marshall BM, Levy SB. Clinical Microbiology Reviews. "Food Animals and Antimicrobials: Impacts on Human Health." October 2011, 24(4), 718-733, doi: 10.1128/CMR.00002-11
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Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.
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