(This story is the first in a series, "Farmaceuticals".)
By Brian Grow and P.J. Huffstutter
ATLANTA/CHICAGO, Sept 15 (Reuters) - Major U.S. poultry firms are administering antibiotics to their flocks far more pervasively than regulators realize, posing a potential risk to human health.
Internal records examined by Reuters reveal that some of the nation's largest poultry producers routinely feed chickens an array of antibiotics - not just when sickness strikes, but as a standard practice over most of the birds' lives.
In every instance of antibiotic use identified by Reuters, the doses were at the low levels that scientists say are especially conducive to the growth of so-called superbugs, bacteria that gain resistance to conventional medicines used to treat people. Some of the antibiotics belong to categories considered medically important to humans.
The internal documents contain details on how five major companies - Tyson Foods, Pilgrim's Pride, Perdue Farms, George's and Koch Foods - medicate some of their flocks.
The documented evidence of routine use of antibiotics for long durations was "astonishing," said Donald Kennedy, a former U.S. Food and Drug Administration commissioner.
Kennedy, president emeritus of Stanford University, said such widespread use of the drugs for extended periods can create a "systematic source of antibiotic resistance" in bacteria, the risks of which are not fully understood. "This could be an even larger piece of the antibiotic-resistance problem than I had thought," Kennedy said.
Reuters reviewed more than 320 documents generated by six major poultry companies during the past two years. Called "feed tickets," the documents are issued to chicken growers by the mills that make feed to poultry companies' specifications. They list the names and grams per ton of each "active drug ingredient" in a batch of feed. They disclose the FDA-approved purpose of each medication. And they specify which stage in a chicken's roughly six-week life the feed is meant for.
The feed tickets examined represent a fraction of the tens of thousands issued annually to poultry farms run by or for major producers. The confidential information they contain nonetheless extends well beyond what the U.S. government knows. Veterinary use of antibiotics is legal and has been rising for decades. But U.S. regulators don't monitor how the drugs are administered on the farm - in what doses, for what purposes, or for how long. Made public here for the first time, the feed documents thus provide unique insight into how some major players use antibiotics.
The tickets indicate that two of the poultry producers - George's and Koch Foods - have administered drugs belonging to the same classes of antibiotics used to treat infections in humans. The practice is legal. But many medical scientists deem it particularly dangerous, because it runs the risk of promoting superbugs that can defeat the life-saving human antibiotics.
In interviews, another major producer, Foster Poultry Farms, acknowledged that it too has used drugs that are in the same classes as antibiotics considered medically important to humans by the FDA.
About 10 percent of the feed tickets reviewed by Reuters list antibiotics belonging to medically important drug classes. But in recent presentations, scientists with the U.S. Centers for Disease Control and Prevention said the use of any type of antibiotic, not just medically important ones, contributes to resistance. They said that whenever an antibiotic is administered, it kills weaker bacteria and enables the strongest to survive and multiply.
Frequent, sub-therapeutic use of antibiotics in low doses intensifies that effect, scientists and public health experts say. The risk: Any resulting superbugs might also develop cross-resistance to medically important antibiotics.
According to the feed tickets reviewed, low doses of antibiotics were part of the standard diet for some flocks at five companies: Tyson, Pilgrim's, Perdue, George's and Koch.
"These are not targeted uses aimed at specific bugs for defined duration. They're multiple, repeat shotgun blasts that will certainly kill off weaker bugs and promote the stronger, more resistant ones," said Keeve Nachman, director of the food production and public health program at Johns Hopkins University's Bloomberg School of Public Health.
"HIGHLY IMPORTANT" DRUGS
This month, Perdue Farms announced that it had stopped applying the antibiotic gentamicin to eggs in chicken hatcheries. Gentamicin is a member of an antibiotic class considered "highly important" in human medicine by the FDA. The company said it wants "to move away from conventional antibiotic use" because of "growing consumer concern and our own questions about the practice."
The move won't change what Perdue feeds its chickens, however. Some of its feed has contained low levels of one antibiotic, feed tickets show. Perdue said it only uses antibiotics that aren't considered medically important by the FDA, and at some farms, it uses no antibiotics at all.
"We recognized that the public was concerned about the potential impact of the use of these drugs on their ability to effectively treat humans," Bruce Stewart-Brown, Perdue's senior vice president of food safety and quality, said when the hatchery policy was announced.
The poultry industry's lobby takes issue with the concerns of government and academic scientists, saying there is little evidence that bacteria which do become resistant also infect people.
"Several scientific, peer reviewed risk assessments demonstrate that resistance emerging in animals and transferring to humans does not happen in measurable amounts, if at all," said Tom Super, spokesman for the National Chicken Council. He said using antibiotics to prevent diseases in flocks "is good, prudent veterinary medicine. Prevention of the disease prevents unnecessary suffering and prevents the overuse of potentially medically important antibiotics in treatment of sick birds."
Poultry producers began using antibiotics in the 1940s, not long after scientists discovered that penicillin, streptomycin and chlortetracycline helped control outbreaks of disease in chickens. The drugs offered an added benefit: They kept the birds' digestive tracts healthy, and chickens were able to gain more weight without eating more food.
Over the years, the industry's use of antibiotics grew. Early on, independent scientists warned that bacteria would inevitably develop resistance to those antibiotics, especially when the drugs were administered in low doses. In 1976, a landmark study by microbiologist Stuart Levy showed that potentially deadly bacteria in poultry were developing resistance to tetracyclines and other antibiotics. The resistant bacteria, E. Coli, were then moving from poultry to people.
That is when the FDA first tried to rein in drug use in food animals. The agricultural and pharmaceutical industries resisted, viewing low-level antibiotic use as a way to produce meat more quickly and cheaply.
Today, 80 percent of all antibiotics used in America are given not to people, but to livestock.
About 390 medications containing antibiotics have been approved to treat illness, stave off disease and promote growth in farm animals. But the FDA has reviewed just 7 percent of those drugs for their likelihood of creating antibiotic-resistant superbugs, a Reuters data analysis found. [IDn:xxxxx]
The widespread use of antibiotics worries public health authorities. In a report this year, the World Health Organization called antibiotic resistance "a problem so serious it threatens the achievements of modern medicine." The annual cost to battle antibiotic-resistant infections is estimated at $21 billion to $34 billion in the United States alone, the WHO said.
Each year, about 430,000 people in the United States become ill from food-borne bacteria that resist conventional antibiotics, according to a July report by the CDC. Overall, the CDC estimates that 2 million people are sickened in the United States annually with infections resistant to antibiotics. At least 23,000 people die.
"That's the number we are certain of. The actual number is higher," said Steve Solomon, director of the CDC's Office of Antimicrobial Resistance.
This year, federal investigators tracking a salmonella outbreak traced virulent strains of the pathogen to chickens raised by Foster Farms, the largest poultry producer on the West Coast.
Investigators identified seven strains of Salmonella Heidelberg that had sickened at least 634 people across the United States and Puerto Rico this year and last. More than 200 of those people were hospitalized, according to the CDC. In July, Foster Farms issued a recall of some chicken products.
When epidemiologists examined 68 of the Salmonella Heidelberg cases linked to Foster Farms, they found that two-thirds of the bacteria were resistant to at least one antibiotic, according to the CDC. Half of these superbugs were impervious to drugs in at least three different classes of antibiotics.
In an effort to stop the spread of resistant bacteria, the FDA has issued voluntary guidelines to regulate antibiotic use by producers of poultry and other livestock. The agency says it also inspects the mills where animal feed is made. It considers those inspections to be a "more effective" use of its resources than examining how farmers administer feed.
Not until 2016 does the FDA plan to gather data about antibiotic use on farms, said Craig Lewis, a veterinary medical officer with the agency. Today, "none of us have an idea first-hand of what's going on" at the farm level, Lewis said this summer, at a public meeting on antibiotic resistance.
Super, the National Chicken Council spokesman, said the information on feed tickets "is available to FDA, the regulators, whenever they want to go see it."
Still, companies are reluctant to discuss how they medicate their flocks.
One, Pilgrim's Pride, said it would take legal action against Reuters unless the news agency gave the company access to Pilgrim's feed tickets that reporters had reviewed. Reuters declined to do so.
The tickets show that Pilgrim's added low doses of the antibiotics bacitracin and monensin, individually or in combination, to every ration fed to a flock grown early this year. Neither drug is classified as medically important by the FDA, although bacitracin commonly is used to prevent human skin infections.
The Colorado-based company wouldn't address questions about its use of antibiotics. Its general counsel, Nicholas White, called the contents of its tickets "confidential business information."
U.S. Sen. Kirsten Gillibrand, D-New York, said the feed tickets substantiate what she long suspected: "that the overuse of antibiotics on many chicken farms is rampant."
Gillibrand has been pushing for regulators to more aggressively monitor low-level doses of antibiotics. Now, Gillibrand said, she hopes "the FDA will use the feed-ticket data obtained by Reuters as a wake-up call to re-evaluate their approach to the regulation of antibiotic use in food production."
So does Rep. Rosa DeLauro, D-Connecticut, a member of a House subcommittee overseeing food safety. Told of the information in the feed tickets, DeLauro called on the FDA to "implement tighter restrictions on antibiotic usage."
All the poultry giants state publicly that they use antibiotics for the limited purpose of keeping chickens healthy.
But the feed tickets, which list the medications included in chicken feed, highlight a second effect of many of the drugs: bulking up the birds.
Some of the tickets reviewed for this article state that the antibiotics promote feed efficiency or weight gain in chickens. The FDA requires companies to list growth promotion on feed tickets whenever feed includes antibiotics that have been approved for that purpose.
Reuters found eight different antibiotics listed on the tickets it reviewed. The tickets come from a scattering of farms across the United States - in Mississippi, Alabama, South Carolina, Virginia and Washington State, among other locations.
George's Inc, a poultry company based in Springdale, Arkansas, issued feed tickets last year to a chicken grower in Virginia. The tickets show that the antibiotics tylosin and virginiamycin were administered solely for "increased rate of weight gain."
Tylosin belongs to a class of antibiotics the FDA considers "critically important" in human medicine, the most crucial of three ranks of sensitive drugs. Virginiamycin is part of a class in the FDA's middle rank, "highly important."
Other George's Inc feed tickets, given to two growers in Virginia this year, show the antibiotics bacitracin and narasin and a non-antibiotic drug called nicarbazin were included in every poultry ration in different combinations until shortly before slaughter. Bacitracin can promote growth.
George's said in a statement: "Occasionally (when necessary to control certain pathogens) appropriate FDA approved medications are utilized to prevent, control or treat specific diseases." It declined to answer detailed questions.
At Tyson Foods, two feed tickets sent by the company to two Mississippi farms show that bacitracin and the non-antibiotic nicarbazin were among the drugs mixed into the feed. The tickets state the drug combination is "for use in the prevention of coccidiosis in broiler flocks, growth promotion and feed efficiency." Coccidiosis is a common intestinal ailment.
Tyson, also based in Springdale, Arkansas, said it does not use bacitracin to promote growth, only to prevent disease. The FDA requires companies to list growth promotion on tickets if medications have that effect, Tyson said. The company said that its feed mixture changes throughout the year. In some seasons, it said, the feed doesn't include bacitracin and nicarbazin.
At Koch Foods Inc, a Chicago-based supplier to fast-food chain KFC Corp, feed tickets contradict a statement on the Koch website about antibiotic use.
Until Aug. 27, the website said Koch Foods uses antibiotics for the narrow purpose of protecting the health of its chickens. "We do not administer antibiotics at growth promotion doses," the statement read in part. "No antibiotics of human significance are used to treat our birds."
Koch feed tickets dated from Nov. 30, 2011, through July 20, 2014, indicate otherwise. They list low-dose amounts of five different types of antibiotics in feed given to flocks at one Alabama farm. One was virginiamycin, in a class considered "highly important" to fighting infections in humans.
In 34 of the 55 Koch Foods feed tickets that Reuters examined, antibiotics at low-dose levels were listed "for increased rate of weight gain," a related growth-promotion use called "improved feed efficiency," or both. Each of those feed tickets also said the antibiotics were for the prevention of coccidiosis, another bacterial infection, or both.
Koch Foods changed the website after being asked by Reuters about its use of virginiamycin. "I regret the wording mistake on that particular letter" on the website, said Mark Kaminsky, Koch's chief financial officer. The company said it is required by the FDA to list certain drugs as growth promoters if they have that effect; Koch says it does not use them for that purpose.
Koch said it has no plans to discontinue the use of virginiamycin, which it says may be used to prevent a common intestinal infection in chicken.
KFC U.S. said in a statement: "KFC's supply partners must adhere to our strict standards and specifications, which in some cases are more stringent than the FDA's regulations." A spokeswoman didn't address detailed questions about antibiotic use by Koch Foods and KFC's other chicken suppliers.
The experience of one grower raises questions about whether preventive use of antibiotics has a meaningful effect on the health of chicken.
Craig Watts, who grows chicken for Perdue, says he sees little difference in outcomes for the birds he raises on feed containing an antibiotic and those he grows for the company's antibiotic-free line.
Perdue mixes the antibiotic narasin into feed given to chickens in the company's antibiotic-fed line. Its antibiotic-free line contains antimicrobial drugs that kill micro-organisms, but none that the FDA defines as an antibiotic, according to Perdue feed tickets shown by Watts. None of the drugs listed by Perdue on the feed tickets is considered medically important for humans.
Watts owns C&A Farms, about 20 miles north of Dillon, South Carolina. Since 2012, he has raised five antibiotic-free flocks for Perdue and seven flocks that received low doses of the antibiotic narasin, according to his records.
The mortality rates of the two flock types were nearly identical. About 900 birds died, per house, on the four-house farm. Flocks that received antibiotics and those that didn't both hit Perdue's target weight of about 4.25 pounds per bird.
Perdue sees "similar" performance among birds fed antibiotics and those that do not receive the drugs, said Stewart-Brown, the Perdue official overseeing food safety. "We feel our current two approaches are both very responsive to public health concerns about antibiotic use in poultry."
Perdue still uses antibiotics in some cases, because antibiotic-free flocks are "more expensive to run and more difficult to manage effectively," Stewart-Brown said. The production complex served by Watts' farm recently transitioned to all antibiotic-free flocks.
TRACKING AN OUTBREAK
One poultry giant whose antibiotic use has come into question is Foster Farms, based in Livingston, California. Its experience shows the difficulty of pinpointing when and how a bacteria turns into a superbug, say federal investigators.
Beginning last year, a salmonella outbreak spread across Oregon, Washington, California and 27 other states and territories. Federal investigators later linked the outbreak to chickens raised by Foster Farms and processed at a trio of its slaughterhouses in central California, according to USDA and CDC officials.
The scope of the outbreak reflected Foster Farms' vast scale. Its operations in California's Central Valley date to 1939, when Max and Verda Foster borrowed $1,000 against a life insurance policy and invested in an 80-acre farm.
Today, Foster owns large tracts of California farmland, chicken hatcheries in Colorado and train cars that haul grain from the Midwest. An estimated one of 10 chickens eaten in the United States is hatched, raised and slaughtered by Foster Farms, according to industry officials. The company dominates the chicken market west of the Rocky Mountains.
As the CDC studied what investigators informally called the "Foster Farms Outbreak," researchers soon made a troubling discovery. Some of the Salmonella Heidelberg strains linked to Foster products proved resistant to a variety of antibiotics, the CDC concluded. Some of those drugs belonged to the same classes as penicillin and chlortetracycline, or CTC.
Some questions remain. Government investigators didn't determine how the Salmonella Heidelberg traced to Foster Farms became resistant to antibiotics, and didn't trace the resistant bacteria to specific farms. They didn't examine Foster feed tickets from the outbreak period to see which antibiotics the company was using and how the drugs were being administered.
Reuters asked to see Foster Farms' feed tickets from that period; the company didn't respond to that request.
Foster Farms said it commissioned research that yielded findings very different from the CDC's. The company declined to share the study. It summarized the research by saying scientists found no antibiotic resistance in two dozen salmonella samples collected from Foster Farms in 2012.
A CDC spokeswoman said the agency is aware that Foster Farms sponsored a study and has asked to review it, but hasn't received a copy.
"BIOLOGY AT WORK"
Foster Farms told Reuters it has administered CTC and penicillin at times, but selectively, not as part of standard feed. Foster said it had used CTC "as needed" to fight bacterial infections. It declined to say where or when it administered CTC. The company said it still uses penicillin to treat sick birds, but only "in critical situations when flocks are exposed to fatal diseases." Foster doesn't use antibiotics as growth promoters, it said.
CDC official Robert Tauxe helped investigate the outbreak. "Use of chlortetracycline could have contributed to the resistance patterns we saw" in the Salmonella Heidelberg, said Tauxe. "Penicillin, too."
On July 11, the CDC said the Salmonella Heidelberg outbreak had ended. The USDA said it is monitoring the company's new salmonella-prevention efforts. Agency officials and Foster's chief veterinarian, Bob O'Connor, said the measures are working.
The company has reduced salmonella-infection rates on chicken meat from its California facilities to less than 3 percent, O'Connor said, far below the national average of 25 percent.
Despite the gains, O'Connor said the challenge of eradicating salmonella in the chicken industry remains. "For the people who wanted a silver-bullet-type story, there isn't one," O'Connor said. "With salmonella, we're not going to be able to say, 'It's over.'"
David Acheson, a former senior medical officer for the USDA and the FDA, now serves on a food safety advisory board for Foster Farms. He said the board never examined Foster's use of antibiotics and whether its practices could have spawned superbugs.
"Does anyone know that it happened? No. Is it possible? Could it have happened? Yes," Acheson said. "We know that antibiotic use, irrelevant of what you are treating, whether it be human or animal, can increase the likelihood of resistance. It's biology at work." (Reporting by Brian Grow in Atlanta and Fairmont, North Carolina and P.J. Huffstutter in Chicago and Livingston, California. Additional reporting by Michael Erman and Eric Johnson. Edited by David Greising and Blake Morrison.)