You Can’t Resist

Antibiotic resistance could bring about the next global crisis—a world where “strep throat … could once again kill,” warns the World Health Organization. Few experts dispute the dangers of infections that cannot be controlled. The question—debated in courtrooms and on Capitol Hill—is whether America’s industrialized farms bear significant blame.

“Lots of resistant bacteria travel from farm to table,” says Tufts microbiologist Stuart B. Levy. Studies have found high levels of resistant bacteria in supermarket samples of beef, pork and poultry that can cause food-borne illnesses in people who mishandle the raw meat or eat it undercooked.

But meat is not the only route of transmission. Resistant strains of bacteria have been found in industrial farm workers and their families; in the air, water and soil around industrial farms; and even in the flies nearby and on cars that have traveled behind trucks bringing animals to slaughter. An estimated 90 percent of antibiotics fed to food animals are excreted in their waste, and that manure is often sold as fertilizer products, some of which are marketed as “organic compost.”

Under fire is a longstanding farming practice of routinely feeding low (“subtherapeutic”) doses of antibiotics to food-producing animals—not because they are sick, but to prevent disease and speed their growth. Chronic exposure to antibiotics in humans, animals and the environment, says Levy, accelerates the creation of resistant bacteria and infections against which the so-called wonder drugs of the 20th century are becoming powerless.

Levy, a modern-day Paul Revere for antibiotic resistance, has been sounding the alarm for more than three decades. He says misuse and overuse of antibiotics by doctors and patients is a major problem. Doctors prescribing antibiotics for viral illnesses such as colds, patients insisting on getting those drugs and patients failing to finish their prescriptions have all given resistant strains a better chance to take hold.

But Levy says the pure volume of antibiotics used on farms—some estimates say 80 percent of the antibiotics sold in the United States are for animals, not people—has scientists concerned about agribusiness’s contribution to a growing public health threat.

“Suddenly we get a report of a bacterial strain that is resistant to eight antibiotics, and you know that that occurred in animals [because it was isolated from meat samples], and it’s shocking that it even occurred,” says Levy, a professor at Tufts School of Medicine, president of the international Alliance for the Prudent Use of Antibiotics based at Tufts and author of The Antibiotic Paradox: How the Misuse of Antibiotics Destroys Their Curative Powers.

Levy says that one multidrug-resistant kind of staph infection—caused by methicillin-resistant Staphylococcus aureus (MRSA)—showed up in hospitals as early as the 1960s, before it and others like it emerged in the general population. “Now different strains are cropping up on farms. This is not a good sign,” he says, because it means resistances in bacteria harbored by animals could transfer to bacteria associated with people.

Unfair Target

Agribusiness, with wide support from veterinarians, has a different perspective. George Saperstein, professor and chair of environmental and population health at the Cummings School of Veterinary Medicine at Tufts, says the industry is unfairly maligned, management practices are misrepresented and charges of antibiotic abuse are often erroneous and exaggerated.

Saperstein believes the industry generally uses antibiotics prudently, primarily to prevent disease from racing through flocks or herds on large-scale farms, which produce much of America’s food. Management practices on such farms have come under fire for years, with charges that antibiotics are excessively and indiscriminately given to food animals so they’ll gain weight and grow faster, reducing costs and compesating for poor nutrition and the cramped, stressful and unsanitary conditions in which food animals spend their lives.

“The statement you hear a lot—that antibiotics are being used to substitute for good management or good sanitation—couldn’t be further from the truth,” Saperstein says. He is not suggesting zero problems or zero risk, but he says management practices at large farms are generally commendable.

While Saperstein acknowledges the presence of antibiotic-resistant bacteria on farms—as well as many other places—he says he has not seen enough “fingerprint” scientific evidence linking significant human disease outbreaks to multidrug-resistant bacteria strains that have emerged solely as a result of farming practices.

He points to a Purdue University study that reviewed Denmark’s experiences since that country phased out antibiotics as livestock growth promoters in 1999. The study suggests that changes in resistance patterns in bacteria isolated from livestock have limited influence on resistance patterns in bacteria isolated from humans.

Saperstein and others are concerned that across-the-board prohibitions of the subtherapeutic use of any antibiotic may make it more difficult for farmers to keep their animals healthy and the food they produce safe and affordable.

Consumers who worry about antibiotics in meat often confuse “residue” with “resistance.” The FDA sets standards to ensure that animals brought to slaughter have undergone withdrawal periods to allow drug residues to clear their systems. Resistance poses different issues: Are there antibiotic-resistant bacteria in the meat that could sicken consumers? And are farming practices a major contributor to the pools of resistant bacteria in the environment?

Potentially a Huge Crisis

All sides agree antibiotic resistance is simply a force of nature. When bacteria are exposed to an antibiotic, some of the microbes are killed, but others—ones with mutations that enable them to resist the drug’s effects—survive and multiply, passing along their protective mutations. The more an antibiotic is used or misused, the more likely new, drug-resistant strains will evolve.

Concerns are intensifying about the speed at which this is happening. Some strains are already resistant to multiple antibiotics. They were perhaps helped along by bacteria’s recently discovered ability to exchange DNA, such that those never exposed to an antibiotic can pick up genetic material from an unrelated resistant strain and mutate into a new strain that is also resistant.

Rebecca Klein, N08, the public health and agriculture policy project director for the Center for a Livable Future at Johns Hopkins Bloomberg School of Public Health, likens aspects of antibiotic resistance to climate change: “It’s relatively slow moving but potentially a huge crisis.”

Klein says consumers unaware that agriculture is implicated in antibiotic resistance are less likely to protest. “There is a certain amount of trust, thinking that if this were really a problem, the government would do something about it. I think if [the public] were more aware, they’d be demanding a shift, and that shift would take place.”

On the list of things to be aware of: The Center for Science in the Public Interest documented 38 food-borne outbreaks between 1973 and 2011 in which the bacteria were resistant to one or more antibiotics. Last year 36 million pounds of ground turkey had to be recalled because of contamination by Salmonella Heidelberg, which is resistant to several antibiotics used in human medicine and in agriculture. That outbreak caused one death and sickened 107 people.

For the past 16 years, the National Antimicrobial Resistance Monitoring System, a collaboration of the Centers for Disease Control and Prevention, the FDA and the U.S. Department of Agriculture, has tracked data to determine whether antibiotic resistance is transmitted to humans through the food supply.

The organization’s 2010 report says more than half the ground turkey samples tested carried E. coli bacteria that were resistant to at least three classes of antibiotics. Nearly 30 percent of chicken breast and ground turkey samples contained Salmonella resistant to five classes of drug, and almost 29 percent of ground beef samples carried Salmonella resistant to six. This means that if a consumer gets sick, there are fewer and fewer drugs to treat them. One strain found in ground turkey samples, Salmonella Albert, was resistant to all eight classes of antibiotics for which it was tested.

Studies have even found significant amounts of resistant bacteria, including MRSA and E. coli, in meat labeled as raised without antibiotics. Some speculate the meat might have picked up the bacteria from workers or at processing plants if the equipment was not sterile. Because the creation and transmission of resistant bacteria amount to an invisible web that scientists are still trying to fully untangle, activists say it’s time to curb antibiotic use on farms and in all of society.

“One of the things we say is that you can’t shop your way out of this problem,” says Sarah Borron, N07, a researcher at the nonprofit Food and Water Watch. “It is important to buy local, organic…and it’s certainly good to support producers who are choosing not to use antibiotics,” she says, but the most powerful avenue for change is in the hands of the government, which can mandate restrictions on antibiotic use.

Where Are the Regulators?

Public health and consumer advocacy groups focused on agriculture’s role in drug resistance are increasingly frustrated by what they say is government’s failure to act, so frustrated that they filed suit in an effort to force more regulation. In March a federal judge sided with those groups and ordered the FDA to follow through on restrictions against two classes of antibiotics widely used in agriculture—tetracycline and penicillin.

More than 35 years ago, the FDA proposed prohibiting the use of these two drugs to promote animal growth because of concerns about antibiotic resistance. But the agency backed off, critics say, because of political and industry pressure. Now the court has ordered the FDA to proceed with that ban, although the drug manufacturers first will have the opportunity to prove their use in agriculture is not creating resistances that are harmful to public health.

In the coming months and years, this and other developments may substantially change how farmers raise the animals that produce our food. In April the FDA announced that it is asking drug makers to voluntarily change the labels that show how their antibiotics can be used on animals, eliminating their use for promoting growth while retaining their use in treating and controlling disease.

And instead of allowing farmers to buy antibiotics over the counter in bulk, as they have done since the 1950s, the FDA is recommending that farmers get prescriptions for the drugs from veterinarians. The aim of these federal “guidance documents” is to compel farmers to prove they need to treat or prevent specific illness in their animals, rather than use antibiotics indiscriminately to boost production. The FDA says it has received commitments from drug makers for its voluntary plan, which would be phased in over three years.

Klein says the federal ruling is encouraging because “historically, it has seemed that the power and money from industry have won out [over] laws and regulations.” She is disappointed, however, that the FDA produced guidance documents, which “are just that, guidance documents. If we are going to protect public health, actual regulations need to be in place with funding to ensure compliance.”

Borron’s assessment is more direct: “Anything less than a complete ban on the subtherapeutic uses of antibiotics in livestock is insufficient.”

At the congressional level, proposed legislation would force the FDA to retract approvals for animal feed uses for any of seven classes of antibiotics determined to create resistances harmful to human health. But the legislation, the Preservation of Antibiotics for Medical Treatment Act, has been repeatedly introduced since 2003 and has yet to make it to a vote. Fingers point at intense lobbying by big agriculture and big pharma.

Also under the microscope are scattered restrictions the FDA has already imposed. In 2005 the agency banned the use of a class of antibiotics called fluoroquinolones in poultry production. The FDA said the drugs’ use in poultry production had spawned foodborne fluoroquinolone-resistant Campylobacter infections in humans, a gastrointestinal illness that can be life-threatening in patients with compromised immune systems.

Just this January the FDA restricted another class of antibiotics, called cephalosporins, from being used indiscriminately in animal agriculture for disease prevention and growth promotion. “It is critical to preserve the effectiveness of these drugs,” the order said. Cephalosporins are used to treat pneumonia, strep throat and other infections in humans.

Yet cephalosporins and fluoroquinolones were not as widely used in animal agriculture as are tetracycline and penicillin. “The FDA seems to be sending mixed signals,” Borron says. “On one hand, it has banned subtherapeutic uses of two major classes of antibiotics [fluoroquinolones and cephalosporins], but it has taken a lawsuit to make the FDA address a proposal to ban the same uses in two other major classes [tetracyclines and penicillins]. And the FDA currently insists that voluntary efforts in cooperation with industry will work, all while new scientific evidence calls into question whether producers are even following the legal bans,” Borron says.

That new evidence, a study released in April by the Center for a Livable Future and Arizona State University’s Biodesign Institute, found that fluoroquinolones are still showing up in feather meal, a byproduct of poultry production used as feed for farm animals and fish.

The study, in which investigators examined samples from the United States and China, found traces of pharmaceuticals and personal-care products, including caffeine and the ingredients in Tylenol, Benadryl and Prozac, which leads George Saperstein, the Cummings School veterinarian, to question whether some of the drugs were introduced not at farms but by renderers who process animal parts into fertilizer and feed.

Saperstein nevertheless advises the farm industry to make changes ahead of regulation: “If the consumer is given the impression that the industry is doing something wrong and the FDA is trying to stop them,” it is more damaging than “proactively saying we’re going to stop using subtherapeutic antibiotics.

“Agriculture has always rapidly responded to consumer preferences. . . . It’s a free-market product,” and farmers want to please consumers, he says. Changes in antibiotic use will create incentives for new technologies and alternatives, including more and better vaccines, he says. But Saperstein worries that some small farmers, especially those in remote locations with less access to a dwindling number of veterinarians who specialize in caring for large animals, might not “survive the shakeout” of certain mandates and financial pressures.

Klein sympathizes with the challenges farmers face. “We need laws that protect human health,” she says, “and we need to find ways to support farmers’ transition to production methods that protect essential drugs and biodiversity.”

The Big, Bad Bugs

Methicillin-resistant Staphylococcus aureus, commonly known as MRSA, kills an estimated 19,000 people in the United States each year and sickens another 76,000. According to the World Health Organization, 440,000 new cases of multi-drug-resistant tuberculosis emerge annually, causing at least 150,000 deaths worldwide.

There are reports that some strains of TB and gonorrhea, which infects 600,000 Americans each year, have rendered ineffective almost all available antibiotics.

Also of concern is the fact that almost no new antibiotics are being developed to replace the drugs that have lost their “firepower,” in the words of Tufts microbiologist Stuart B. Levy, an international expert on antibiotic resistance.

While 13 classes of antibiotics were created between 1935 and 1968, only two new classes have been developed in the 44 years since, as major pharmaceutical companies invest in drugs for such chronic conditions as high cholesterol, arthritis and depression.

At a congressional hearing in March on legislation proposed to provide incentives for developing new antibiotics, the Infectious Diseases Society of America reported “an increasing number of patients with serious and life-threatening antimicrobial-resistant infections…against which we have frighteningly few effective therapeutics available.” 

This article first appeared in the Summer 2012 Tufts Nutrition magazine.

Linda Hall is a freelance writer in Hopkinton, Mass.