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cultivating resistance
Some experts estimate more than half of the antibiotics produced in this country are fed to farm animals, mostly to boost their growth rate. In this excerpt from her book Secret Agents, Madeline Drexler chronicles how that practice has led to strains of drug-resistant bacteria, forcing doctors to prescribe higher and higher doses of medicine to combat these more resilient pathogens. "Farms are some of the most insidious sources of antibiotic resistance," Drexler writes. "Whether carnivore or vegetarian, you cannot avoid the aftermath of antibiotics applied lower in the food chain." A former medical columnist for The Boston Globe, Drexler was a Knight Science Journalism Fellow at the Massachusetts Institute of Technology from 1996 to 1997.

An excerpt from Secret Agents: The Menace of Emerging Infections by Madeline Drexler, published by the Joseph Henry Press (2002). Reprinted by permission. To read the full text online, go to http://www.nap.edu/.

cover of Secret Agents: The Menace of Emerging Infections Not all resistant microbes spring from misguided human medicine. Farms are some of the most insidious sources of antibiotic resistance. As mentioned in Chapter 3, antibiotics are routinely fed in tiny amounts to farm animals -- not to fend off disease, but to boost growth. And low-level use of antibiotics is a perfect way to foster resistant organisms. In recent years, livestock industry experts had estimated that 40 percent of antibiotics produced in the United States went to farm animals. In 2001, however, a report from the Union of Concerned Scientists, a Cambridge, Massachusetts-based environmental advocacy group, raised this estimate to a whopping 70 percent. Public health experts have long worried that farmers are squandering human life-saving drugs on animals that are not even sick.

Take Campylobacter, the most common bacterial cause of foodborne illness. In 1995, American poultry farmers began using a fairly new class of drugs known as fluoroquinolones to treat respiratory infections in poultry. In people, these broad-spectrum, low-toxicity drugs are some of the most prized antibiotics today, because they are slow to breed resistance and are effective against some of the hardest-to-treat infections. Almost immediately after poultry farmers began dosing their birds with the medication, thousands of people who ate undercooked chicken contaminated with fluoroquinolone-resistant strains of campy themselves became infected with the drug-resistant bacteria. Before the drug was used, no Campylobacter specimens cultured from hospital patients had been resistant; today, nearly a fifth are, and the figure is sure to rise.

Even more dangerous than drug-resistant Campylobacter is resistant Salmonella, which is also present in poultry and meat. In human medicine, fluoroquinolones are the preferred treatment for invasive, and often life-threatening, Salmonella infections. Yet today, doctors are resorting to higher and higher doses of fluoroquinolones to treat Salmonella -- a possible prelude to full-blown resistance. And now there's a frightening new wrinkle in treating the organism. In 1998, a 12-year-old Nebraska boy picked up a Salmonella infection from his family's cattle that was resistant to ceftriaxone -- one of the cephalosporin class of antibiotics -- as well as a dozen other antibiotics. Fortunately, he survived when doctors treated him with a combination of other drugs. But when this unprecedented case was reported in 2000, it terrified public health officials. Ceftriaxone is one of the few antibiotics that reliably kills most bacteria. And it is the drug of choice for children whose Salmonella infections have entered the bloodstream -- a condition that kills about 1,000 Americans every year. Ceftriaxone is also the drug that doctors turn to when treating young victims; because of worries about bone growth, quinolones are not approved for children. Since 2000, more cases of ceftriaxone-resistant Salmonella in people have turned up. "This Salmonella is so multiresistant," says the CDC's David Bell, "there are no good drugs left that are approved for children." To history-minded physicians, the situation evokes futile attempts at the turn of the last century to treat typhoid fever, another Salmonella infection. Extrapolating from subsequent studies of patients, health officials calculate that tens of thousands of Salmonella cases each year are ceftriaxone-resistant. The clinical problem also touches on a moral quandary: ceftriaxone is not used as a growth promoter, but rather to treat sick animals. "It portends a dilemma," says the CDC's Fred Angulo. "Societally, what do you want to do: treat sick people or sick animals?"

Another foodborne infection is VRE -- yes, the same bug that wreaks so much havoc in critically ill hospital patients. In this country, VRE isn't primarily foodborne; the organism is most often bred by massive vancomycin use in hospitals. It's a different story in Europe. Soon after farmers there began feeding avoparcin, a growth promoter related to vancomycin, to livestock in 1974, the animals developed vancomycin-resistant enterococci. (Because it may be a carcinogen, avoparcin never received approval in the United States.) In 1986, France found its first human patient with VRE. Within a few years, the bacterium spread throughout human intestinal tracts on the Continent. U.S. public health experts believe that at least some of the VRE organisms in this country may have come from Europe and then proliferated under the selective influence of vancomycin in hospitals here.

But while foodborne vancomycin-resistant enterococcus infections are uncommon in the United States, a similar chain of events is starting to happen here with another drug. For more than a quarter century, American poultry farmers have used the growth promoter virginiamycin in chicken feed. In chickens, the drug helped breed enterococci that are resistant to virginiamycin's human-use cousin, Synercid. Synercid is the other "last-resort" antibiotic, approved for humans in 1999. Yet as a frightening presentiment to the drug's potential downfall, more than half of grocery-store chickens carry bacteria impervious to this end-of-the-line human drug. People are picking up these resistant bacteria in their meals. At any one time, at least 1 percent of the U.S. population is carrying Synercid-resistant enterococci. Usually, these intestinal bacteria are expelled as food moves through the intestines, never causing a problem. But in the rare instance that such an individual enters the hospital -- say, for a hip replacement -- and happens to be treated with Synercid, the resistant enterococcal bacteria in the gut will go wild, threatening an infection that no antibiotic can quell.

One of the most frightening and enigmatic foodborne pathogens is a drug-resistant strain of Salmonella typhimurium. Known as Definitive Type 104, or DT 104, it defies five important classes of drugs in the United States; in Europe, where it surfaced in 1984, it thwarts seven. This monster resistance has helped it spread in cattle, because in animals that receive any one of these drugs, DT 104 gains an advantage. In the U.S., hundreds of thousands of people suffer DT 104 infections annually. Raw milk is a common culprit, the bacterium having infiltrated dairy herds. In 1997, for example, more than 100 Californians became sick from DT 104 in two overlapping outbreaks in Hispanic communities, where residents ate homemade Mexican-style cheese made from unpasteurized milk and sold by street vendors and specialty markets.

When scientists tried to figure out where this renegade came from, they were shocked. DT 104's resistance genes were a strange combination -- so strange, they had never before been seen in Salmonella. Where they had turned up was worlds away: in Asian aquaculture, where fish have been regularly treated with antibiotics since the early 1980s. So how did they land in the American heartland? One theory holds that some of those Asian fish may have been ground up into fish meal, an international commodity often fed to pigs and poultry. Or DT 104's resistance genes may have found their way into animal breeding stock, perhaps through the rendered protein of other animals. However it happened, DT 104 appeared more or less simultaneously around the world in the 1980s, suggesting that the animals acquired these alien bacteria en masse.

In 1969, Britain's Swann Committee concluded that antibiotics used in human therapy or those that promote cross-resistance in people should be banned from animal growth promotion. Unfortunately, livestock producers hew to the position that whatever drugs they feed their animals are proprietary secrets. Besides, say industry officials, they need antibiotics to produce safe and affordable food. A 1999 report published by the Institute of Medicine and the National Research Council questioned this claim. Using the livestock industry's own estimates, the report calculated that if farmers quit using antibiotic growth promoters, the added costs would be less than $10 per American consumer per year. And a 2001 United States Department of Agriculture report showed that hog farmers actually lose money by giving pigs antibiotics that promote growth; while animals do fatten up more, the extra poundage expands overall supply and drives down market prices.

Poultry and livestock aren't the only creatures being dosed with drugs. Salmon, catfish, and trout on domestic fish farms get antibacterial drugs in the water. Honeybees get antibiotics in their hives. And each year, an estimated 300,000 pounds of antibiotic pesticides drift down on fruit trees and other crops to control or prevent bacterial infections such as fire blight. That disease is caused by the pathogen Erwinia, a bacterial cousin of E. coli, Salmonella, and Shigella. Erwinia now resists both streptomycin, an old drug, and tetracycline. Researchers don't know if the fresh fruit invitingly stacked in your supermarket is delivering drug-resistant genes to your intestines. According to microbiologist Abigail Salyers, both the use of untreated or partially treated water for irrigation or for washing vegetables, or the use of manure as a fertilizer for vegetables and fruits could contaminate food plants with antibiotic-resistant bacteria. Proving that no good deed goes unpunished, a 1993 study found higher levels of multidrug-resistant bacteria in intestines of vegetarians than in meat eaters. Whether carnivore or vegetarian, you cannot avoid the aftermath of antibiotics applied lower in the food chain.

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