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From: Food Quality & Safety magazine, December/January 2006

Emerging Resistance

by John Connolly

Ours is the first generation to have the means of protecting itself from the most deadly and common infectious diseases like malaria, tuberculosis, HIV, pneumonia and measles. These diseases can be treated with lifesaving drugs, interventions and control strategies that previous generations could only dream about.

No one knows for sure how many antibiotics used in this country are consumed by animals being raised for food — cattle, dairy, cows, pigs, poultry — but one estimate has the number at 20 million pounds annually. Most of the antimicrobials given to food-producing animals are not used to treat sick animals. Instead, these antimicrobials are routinely added to the feed to prevent disease and promote growth. This exposure to antimicrobials has resulted in resistant bacteria.

Figure 1

When we talk about antibiotic resistance issues, what researchers mean is that bacteria can evolve in animals to become resistant to antibiotics. If humans are exposed to these bacteria they may develop infections that could be difficult to treat. This difficulty in finding treatments is thought to be at least partly due to overuse of antibiotics in humans. The practice of giving antimicrobial doses to prevent disease and promote growth in the animal food supply goes back to the 1950s. Surprisingly, these mechanisms to promote a safe food supply have never been fully understood and are still debated by scientists today.

“The increase in bacterial resistance to antimicrobial drugs is a natural phenomenon — an outcome of evolution,” says Linda Grassie, of the FDA’s Center for Veterinary Medicine (CVM). “Any population of organisms — including bacteria — naturally includes variants with unusual traits. In this case, some bacteria have the ability to fend off the action of an antimicrobial, complicating clinician’s efforts to select the appropriate treatment.”

Food animals, she explains, carry organisms that can make people sick, but may not necessarily make the animals sick. While, Salmonella, Campylobacter and E. coli 0157:H7 are commonly found in the intestines of various food animals, these bacteria may not cause illness in animals, but all three bacteria can cause foodborne illness in humans.

“These bacteria develop resistance when exposed to antibiotics given to the animal,” she says. “These bacteria potentially cross contaminate meat at slaughter and then infect humans who eat the meat, particularly if it is undercooked or cross-contaminated after cooking.”

Figure 2

Is Banning Antimicrobials in Animal Feed The Answer?

The impact of such a ban needs to be studied for issues such as incidence of disease in flocks without preventative antimicrobial treatments, the effect on food production and the general food supply, and how to address possible economic losses to farmers.

Several European countries have already banned the use of antimicrobial treatments in their food animals. In 1986, Sweden banned antimicrobial growth promoters. In 1998, the European Union banned four growth promoters — tylosin, spiramycin, bacitractin, virginiamycin — all similar to human drugs. In 1999, Denmark stopped using growth promoters in chicken, beef, and swine; the result was a 60 percent drop in total volume of antimicrobials used in Denmark (see chart page 52). When these EU countries cut their antimicrobial treatments of food animals, resistance rates fell dramatically. The Centers for Disease Control and Prevention (CDC) recently stated that those who make their living in agriculture must do three things to help stem the advance of antimicrobial resistance in

American food animals:

Reduce use in livestock and in other agriculture production ventures since resistance factors can pass through food to consumers.

Support research for non-antimicrobials to enhance growth in food animals.

Follow the new guidelines from the American Veterinary Medical Association (AVMA) for drug use for food animal veterinarians.

Many scientists are concerned about potential problems from the relationship between the use of the agents in food-producing animals and the emergence of Salmonella serotypes with reduced suspecitibility to flouroquinolones in humans. Since its introduction into poultry, there has been a significant increase in flouroquinolone resistant Campylobacter Jejuni isolated in live poultry, poultry meat, and humans in the U.S., U.K. and Holland. Surveillance for antimicrobial resistance is being expanded and an FDA study will soon be launched of resistant pathogens found in retail foods. One of the big concerns raised is that reducing antimicrobial use in food animals will cause production costs to rise considerably.

Figure 3

“The experience of the European Union with respect to withdrawal of approval for use of sub therapeutic antibiotics needs to be closely scrutinized,” said Randy Huffman, Ph.D., vice president of Scientific Affairs at the American Meat Institute Foundation.

“When meat and poultry are produced under federal inspection and prepared properly at home, these products are very safe — among the safest meat products in the world.”

Currently, he says, the scientific community believes that bacteria that have genetic traits that allow resistance to antibiotics are not any more hardy to the normal handling and cooking practices that U.S. manufacturers and consumers use every day to ensure food is safe to eat.

“There is no evidence to conclude that bacteria become more resistant to normal cooking temperatures just because they have developed genetic resistance to a certain class of antibiotics,” Huffman says. “Proper cooking will ensure safety all the time.”

In July 2005, the FDA announced it would no longer allow the distribution of enrofloxacin for the purpose of treating bacterial infections in poultry. Enrofloxacin — a fluoroquinolone — is marketed under the name Baytril by the Bayer Corp. Scientific data collected by the FDA indicated that use of the drug encouraged resistance to Campylobacter, a foodborne illness usually harbored in the intestines of poultry. Baytril is a close cousin to the human antimicrobial Cipro. So, the question begs — are poultry products a more risky food in terms of harboring bacteria? Does any one animal food pose more of a danger than another?

“This is an important question but difficult to answer,” said Dr. Tom Chiller, chief medical epidemiologist for the Foodborne Diseases branch of the Centers for Disease Control and Prevention (CDC). “We are currently working on trying to understand how to estimate and attribute foodborne illness to specific sources. If we look at the retail meat surveillance done by (FDA-CVM), we see that poultry meat purchased from grocery’s have a much higher prevalence of Salmonella and Campylobacter than do ground beef and pork chops, but having the higher prevalence does not mean that there are higher infection rates. This kind of data is being put together by an attribution group and hopefully there will be some estimates coming out next year.”

How Resistance Traits Spread

Many disease-causing organisms have the ability to defend themselves. There are two basic events that occur for resistance to develop and cause a problem; first there is the emergence of the resistance and then the dissemination. Through the process of mutation or gene transfer, bacteria can become resistant to the effects of antibiotics, allowing them to thrive even when a person or an animal takes an antibiotic. For example, frequently exposing a person or an animal to an antibiotic will kill susceptible bacteria in the body, but a small mutation in the genome of other bacteria may allow them to become resistant or escape the effects of the antibiotic. If this happens, antibiotic-resistant bacteria can soon outnumber the antibiotic-susceptible bacteria. This increases the chances for a person or an animal to develop an infection caused by a resistant organism, rather than an antibiotic-susceptible one. Since bacteria between are frequently transmitted between people, between animals, and in some cases, between animals and people, people and animals who have not taken antibiotics may still become infected with antibiotic-resistant bacteria. Depending upon the types of resistance that develop, it may be difficult to treat an antibiotic-resistant infection, requiring additional antibiotics and more expensive treatments.

More than a dozen federal agencies have an interest in the problem of antimicrobial resistance, and several of these agencies have responsibilities regarding the use of antimicrobials in agriculture. Coordinated interagency efforts toward an effective public health response to the problem began several years ago. The FDA’s CVM collaborates with the CDC, as well as the USDA to monitor antimicrobial resistance among enteric bacteria in humans, animals, and retail meats through a surveillance program called NARMS (National Antimicrobial Resistance Monitoring System).

CVM has developed guidance for industry that outlines a risk assessment approach for evaluating the microbial food safety of antimicrobial new animal drugs and possible risk management steps. In addition to work being done by CVM, veterinary practitioner groups, and producer groups have developed prudent and judicious antimicrobial drug use programs to help vets and producers make safe and sound decisions about the use of these products in animal production.

“Bacteria are resilient and will develop the ability to survive in harsh conditions, such as exposure to an antibiotic challenge,” says AMI’s Huffman.” The emergence of antibiotic resistant organisms is not a new phenomenon and has been recognized for 50 years, interestingly not long after penicillin became widely available. With increased use of a variety of antibiotics, both for treating humans and animals, the development of resistance have increased.”

For more information please contact Larry Hollis, antimicrobial researcher at Kansas State University, 785-532-1246, Tom Chiller, MD, chief medical epidemiologist, Foodborne Disease Branch, Centers for Disease Control, 404-371-5406, Linda Grassie, Food and Drug Administration, at Linda.Grassie@fda.gov or Randall Huffman, Ph.D., v.p. Scientific Affairs American Meat Institute Foundation, 202-587-4233, rhuffman@meatami.com.

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