Agricultural, Environmental, and Community Sources of Resistance

A new study from the Johns Hopkins Bloomberg School of Public Health gives further evidence that antibiotic resistance is only just the result of antibiotic use and abuse in human medicine, but that a reservoir of resistance, from farm animals and environmental contamination, is a significant contributor as well. A team of scientists led by Henry D. Kalter examined E. coli samples in more than 500 young Peruvian children, then compared resistance levels to a range of factors in the children's households and communities. The results are published in this month's issue of the American Journal of Tropical Medicine and Hygiene.As would be expected, the children's own use of antibiotics, as well as family member use, was a significant risk factor for their carriage of drug-resistant bacteria. Applying an antibiotic to a population of bacteria selects for the resistant ones to survive, and though these bacteria might not immediately cause disease, they may pass these genes to other species of bacteria, for example through conjugation.

But the authors also found evidence for a transfer of resistant bacteria between food animals and humans - specifically, through market chicken raised with antibiotics. Living in a community with more families raising chickens, as opposed to buying their chicken at a market, was a significant protective factor against children's carriage of resistant bacteria. Market chickens were also significanlty more likely to carry antibiotic-resistant bacteria than home-raised chickens, and presumably transferred this resistance to humans in the community though the food chain or direct contact. Dr. Edward T. Ryan, president of the American Society of Tropical Medicine and Hygiene, explained the study's importance in this respect:

"[The study] improves our understanding of the growing global public health threat of antibiotic resistant organisms, and underscores the critical role that antibiotic use in animals plays in contributing to this threat. The vast majority of the tons and tons of antibiotics ingested each year on this planet are administered to livestock and animals. This study clearly shows that such use comes with a very real cost to human health."

The study also identified a link between environmental contamination with antibiotic-resistant bacteria and increased carriage of resistant E. coli. In fact, as the authors write,

"In these poor communities in a developing country, with inadequate protection of excreta and water, contamination of the environment with antibiotic-resistant bacteria appeared to play at least as great a role in children's carriage of resistant E. coli as did the children's own antibiotic use."

These results corroborate the need for a big-picture approach to addressing antibiotic resistance in both developing and developed nations. The authors cite the intensive use of antibiotics on chickens raised in Peru as a factor contributing to resistance in humans there, but this is hardly an isolated issue - millions of pounds of antibiotics are administered to farm animals every year in the United States, and the presence of an environmental and agricultural reservoir of resistance genes is a threat to the success of antibiotic treatment everywhere.

In the News: Antibiotics and Farm Animals

Is the use of antibiotics in farm animals contributing to resistance in humans? That depends on who you ask, but increasing evidence seems to be pointing towards a connection. The long-term, low-dose courses of antibiotics used in almost all farm animals in the United States create an ideal environment for the selection of resistant bacteria, which studies show can be passed to humans through food consumption and direct animal contact. After a ban on all antibiotic growth promoters was implemented in the European Union four years ago, U.S. regulators still waver on their policy stance - with much pressure from the food production industry to leave drug choices up to the farmers themselves.

The issue has been getting increased coverage in news outlets recently. Last month, Katie Couric reported on the link between antibiotic use in animals and human health and on the ban of antibiotic growth promoters in Denmark, the first of the EU nations to institute strict regulations on non-therapeutic drug use in animals. Couric quotes Stephen McDonnell, CEO of Applegate Farms, on the necessity of tighter restrictions on American food producers:

"We use too many antibiotics, we use too many growth promotants. The singular focus is to create cheap meat. That's not always the best thing for the health of the Americans who buy it. We think with some subtle changes - giving [farm animals] more space, feeding them a good diet, and not stressing them out by growing them too quicky - you don't even need to use antibiotics."

Response to Couric's reports was swift. H. Scott Hurd, Director of the WHO Collaborating Center for Risk Assessment and Hazard Identification in Foods of Animal Origin, picked apart her evidence with arguments against a ban on growth promoters. These opposing positions represent the back-and-forth that is behind a bill in the U.S. Congress, PAMTA, which would ban antibiotics as growth promoters. But both sides often suffer from the same lack of evidence: while antibiotic use and resistance surveillance is common in Europe, the U.S. does not monitor the amount of antibiotics fed to farm animals.

In the last week, national columnists have also chimed in on the issue. Nicholas Kristof of The New York Times recounted the story of a California executive stricken with antibiotic-resistant Escherichia coli and attributed increasing resistance to antibiotic use on factory farms, as well as overprescribing by doctors. Yesterday, veterinarian Patty Khuly published an op-ed in USA Today supporting a ban and justifying potentially negative economic and animal health consequences. Like many other experts, she sees overuse of antibiotics in food animal production as part of a larger problem:

"After all, antibiotic use in animal agriculture makes sense primarily because of how we crowd and transport creatures. Remove the antibiotics, and more animals will surely get sick in the short term. But long-term, that only means the industry will be forced to reform how it houses and ships its 'widgets.'"

Antibiotic Resistance 101

Antibiotic resistance is an inevitable result of the use of antibiotics, and is not a new concept. Even in the 1940’s, when penicillin was first mass-produced, resistant bacteria were recognized. But misuse and overuse of antibiotics both create added pressure for the development and spread of resistant bacteria, resulting in reservoirs of resistance that threaten treatment success in all regions of the world.

Acquired antibiotic resistance is the result of a genetic mutation that changes the way a microbe responds to a drug made to eradicate it. These responses vary greatly – for example, some genetically resistant bacteria have altered binding sites so that prevent antibiotic molecules from attaching to cell walls, others have mechanisms to pump out antibiotics when they do get inside.

Even before an antibiotic is administered, a portion of a bacterial population may be genetically resistant to that antibiotic. But adding a drug to the mix puts selective pressure on the community, killing those bacteria that are susceptible but allowing resistant bacteria to survive and multiply. This is especially a risk when antibiotics are administered at low doses not strong enough to wipe out whole populations, or when antibiotic therapy is initiated but then terminated before it can run its full course of wiping out an infection. This leaves lingering populations of bacteria that have been exposed to the drug and given the opportunity to develop resistance. Without susceptible bacteria to compete with, antibiotic-resistant bacteria can quickly multiply and develop into an infection that is no longer treatable by the usual drugs, requiring more aggressive treatment or sometimes leaving doctors with no options – especially in developing nations, where drug access is often limited.

Diagram credit: http://microvet.arizona.edu/Courses/MIC438/decker/
AntibioticRes/AntibioticResistance.html

Genes conferring antibiotic resistance can also propagate in commensal (non-disease causing) bacteria, which are native to all humans, and then be transferred to pathogenic bacteria through conjugation. Both commensal and pathogenic resistant bacteria can be spread through the food supply (e.g. Escherichia coli), or between humans in clincal or community settings (e.g. methicillin-resistant Staphylococcus aureus, or MRSA). These resistant strains are an increasing medical and economic concern - MRSA alone kills 19,000 Americans every year, and one recent study found that antibiotic-resistant infections cost the U.S. healthcare system more than $20 billion annually. The CDC and WHO both rank antibiotic resistance as one of the top three public health concerns worldwide.