Why Antibiotics Are Failing Us

July 1, 2014

 

The road to Dale Krahn’s Abbotsford farm is known as Avenue Zero, and it traces the Canada/U.S. border. In two massive barns Krahn raises about half a million chickens each year. Chicks arrive aboard trucks in batches of 70,000. For the next six weeks, they’re grown with a careful mixture of food, water, and some of the most miraculous drugs ever invented. Then they’re trucked away to be slaughtered, and the next batch arrives. That’s been the routine here for almost 50 years. So when you point out that due to U.S. laws restricting farmyard drug use Krahn’s operation would be illegal 200 metres south, he does a double take. “It sounds a bit weird when you put it that way.”

On a freezing morning last winter, the electric heaters are working hard in Krahn’s barns. When he pulls open a window, fetid air blasts out from the vast carpet of yellow birds. Startled, a clutch of chickens flaps away, revealing a floor caked with a month’s worth of excrement. Normally, when tens of thousands of birds are jammed together in such conditions, sickness and death abound. But these chickens are protected, Krahn explains, by those same miraculous drugs.

The first dose came before the chickens were even born, when the eggs were injected with an antibiotic known as cephalosporin, which is widely used in hospitals to defeat life-threatening infections in humans. The second dose came in their water, which is often laced with fluoroquinolone, another highly prized antibiotic. The next came in the chickens’ food, which can contains yet more antibiotics such as penicillin, whose 1928 invention launched a blessed era of unprecedented health for humanity.

Scientists warn this blessing is fading due to drug misuse on farms and in hospitals. As bacteria evolve to develop resistance to antibiotics, they note, the era of antibiotic medicine — in which billions of people have been saved by these cheaply made wonder drugs — is ending. The reasons are many and complex, but one is apparent in farms across the Fraser Valley’s agricultural belt: chicken farms, and chicken meat, are hotbeds for the rise of drug resistance in bacteria. The farmers say the responsible use of some drugs allows them to deliver a safe, quality product to consumers, and that there are many other, more important threats to antibiotics than chicken feed. Yet the chickens weren’t drugged because they were actually sick, Krahn observes. “These drugs are used to prevent the flock from becoming sick,” he explains. “And to help them grow.”

A rash of health scandals involving antibiotic-resistant bacteria has pummelled the poultry industry. Last December, Consumer Reports revealed that about half of the raw chicken breasts in a U.S. sampling carried antibiotic-resistant “superbug” bacteria. The group said it tested for six types of bacteria in 316 raw chicken breasts purchased from retailers nationwide last July. Some 49.7 percent carried a bacterium resistant to three or more antibiotics, according to the group, and 11 percent had at least two types of bacteria resistant to multiple drugs. Resistance was most common for the antibiotics used for growth promotion and disease treatment in poultry.

According to the Centers for Disease Control and Prevention in Atlanta, Georgia, two multistate outbreaks of Salmonella infections since 2012 sickened more than 15,000 people. In a major report on antibiotic resistance released last year, the CDC said at least two million Americans fall ill from antibiotic-resistant bacteria every year and that at least 23,000 die from those infections. The report estimated that more than 70 percent of antibiotics in the United States are given to animals to prevent sickness when they are packed together in ways that breed infection and to make them grow faster. The report said that “much antibiotic use in animals is unnecessary and inappropriate and makes everyone less safe.” It also said that about half of antibiotic use in people is inappropriate.

Amee Manges, a UBC public health professor who studies urinary tract infections, hypothesizes that poultry is an important vehicle that allows resistant bacteria to move to humans, taking up residence in the body and sparking infections when conditions are right. The genetic type of E.coli that is circulating from food-animal sources and the E.coli causing UTIs are very closely related genetically, Manges noted in a pair of recent studies. Poultry, she says, is the most “problematic” type of meat for drug resistance affecting humans.

The human impacts of these bacterial scourges are far from remote, says microbiologist and infectious diseases physician Jennifer Grant, who heads Vancouver General Hospital’s antimicrobial stewardship team. After reviewing a batch of bacterial resistance updates on a recent afternoon, Grant, who is among Canada’s most outspoken experts on antibiotic resistance, expresses particular worry about a category of bugs known as Extended Spectrum Beta Lactamase Producing Bacteria. These so-called ESBLs are resistant to cephalosporins, the workhorse antibiotics used to treat many serious infections in humans — and on chicken farms as well. “When I first came to VGH in 2006 we rarely saw cephalosporin resistance,” Grant recalls. “Now we see it far too often.” To back that up with data, she scrolls through a set of online charts in her cramped office in Canada’s second-largest hospital. “The resistance levels have increased about 10 percent over five years. That’s not a good trend.” Patients are already suffering the consequences, Grant notes. “If patients can’t be treated with standard drugs like cephalosporins, we begin looking at things that are very toxic, that tend to hurt patients’ kidneys. This is hurting patients every day.”

One of the vectors for antibiotic-resistant bacteria is unrestricted drug use in other parts of the world. When infected people travel, they unwittingly become bacterial couriers. New Delhi Metallo-beta-lactamase-1 was first detected in a patient from India who checked into a hospital in Sweden in 2008. NDM-1 is fearsomely resistant to all known antibiotics, including carbapenums, which are considered the drugs of last resort, when all the others — including the all-important drugs used on farms — have failed. From its springboard in the vast slums of New Delhi, where antibiotics are widely sold from roadside kiosks without medical oversight, NDM-1 has rapidly permeated Asia, Europe, and the Americas.

Treating carbapenum-resistant patients is complex and expensive, the risk of death high. A nationwide outbreak in Israel in 2007 infected as many as 1,250 people, with up to 40 percent mortality. An outbreak last year among patients at Surrey’s Royal Columbian Hospital drove home the message: antibiotic resistance is a worldwide problem capable of severely disrupting health care as we know it. According to the World Economic Forum’s “Global Risks 2014” report, released this January, antibiotic resistance is a risk on par with “large scale terrorist attacks.” Dame Sally Davies, the U.K.’s chief medical officer, speaks of an “apocalyptic scenario” in which people going in for simple operations in 20 years’ time will die of routine infections “because we have run out of antibiotics.” Davies notes that before the antibiotic era six times as many Britons died of infections. “We risk returning to a situation like that,” she warns. “And the stupidity is, we don’t have to.”

Such loosely regulated antibiotic use, whether in communities or on farms linked to cephalosporin resistance in humans, remains little understood and woefully underestimated, Grant says. “We’re dramatically tightening up controls on medical usage of antibiotics,” she says. “And we think it’s long overdue that farmers did the same.”

There are striking numbers indicating that Vancouver’s most dangerous drug problem isn’t heroin or cocaine; it’s antibiotics. Those numbers come from a little-known federal surveillance network called the Canadian Integrated Program for Antimicrobial Resistance Surveillance. Based in Guelph, Ontario, CIPARS tracks the levels of antibiotic resistance in bacteria on retail meat and poultry purchased in grocery stores across Canada. It was data from CIPARS that linked drug use on poultry farms in Quebec to antibiotic resistance in humans: in 2005, government scientists linked cephalosporin injections at Quebec hatcheries to elevated rates of drug-resistant bacteria on chicken sold in Quebec grocery stores, which in turn was associated with elevated rates of drug resistance among Quebec patients. In recent years, CIPARS has published even more troubling data from B.C. In 2012, it recently reported, 39 percent of generic E.coli bacteria on B.C. retail chicken — a staggeringly high rate — was resistant to cephalosporin antibiotics. That’s twice as high as the levels of resistance in E.coli in Quebec, where farmers moderated their drug use after it was locally linked to human resistance. In Salmonella bacteria sampled on B.C. poultry in 2012, 86 percent were cephalosporin-resistant, nearly three times Quebec’s levels.

The Public Health Agency of Canada, the federal agency that operates CIPARS, would respond to questions only by email. Spokesperson Stephane Shank said it is concerned about Category 1 drugs — including the cephalosporins and fluoroquinolones — used on farms. At a conference in Toronto in late 2011, Rebecca Irwin, CIPARS’s senior scientist, went much further in signalling concern about the soon-to-be-published B.C. data, publicly rebuking farmers for keeping information about the drugs they use secret. “We are often in the dark” about the extent of drug use, including the use of drugs for purposes not approved by regulators, Irwin complained. “We have fractured, sparse data.” After denying CIPARS researchers access to data on drug usage for more than a decade, the Chicken Farmers of Canada, which represents 2,700 farmers nationwide, agreed in 2013 to participate in on-farm surveillance, including sharing drug usage information with CIPARS; public disclosure of some data may begin this year. Recently, Health Canada issued a vague media release endorsing support for veterinary oversight of medically important antibiotics, as well as the phasing out of growth-promotion claims. No timeline is specified, nor is any firm regulatory action endorsed.

In the meantime, Canadians seeking to measure farmyard drug use can look to figures from the U.S. and Europe. The Food and Drug Administration, the U.S. department that regulates human and veterinary drug use, says American sales of food-animal antimicrobials — most, but not all, of them medically important — climbed four percent between 2009 and 2011. Sales to livestock and poultry producers of tetracyclines, a class of antibiotics important for treating infections in humans, grew 22 percent during that period. (At the same time, annual American production of cattle and swine remained unchanged, and poultry production rose just four percent.) In Europe, a study from Denmark’s National Food Institute found that before Denmark phased out the use of antibiotics for growth promotion (rather than for treating illnesses) in 2000, about two-thirds of antimicrobial use in pork and 90 percent in poultry production was for promoting growth. Most of the drugs used were human antibiotics. In an indication that the U.S. and European numbers are relevant, the Canadian government estimates that more than three-quarters of all antimicrobials consumed in Canada are used in animals, and approximately 90 percent of these are used to promote growth or prophylactically to guard against disease and infection.

Few people know more about the B.C. CIPARS data than Craig Stephen, a UBC public health professor who founded the Centre for Coastal Health in Nanaimo, which helps collect retail poultry samples for CIPARS. Although he hesitates to blame individual farmers for a problem he views as based on a societal pact between consumers and producers of cheap food, he worries that for the present “We’re stuck with very crude accountability” for drug usage on factory farms — much of which, he explains, is not supervised by veterinarians and does not require mandatory reporting.

For decades, he explains, farmers and government have viewed drug use data as confidential business information. When Stephen himself sought better data from the industry he was threatened with legal action. “I thought it was entirely inappropriate,” he says, “yet this remains the status quo.” For now, he explains, it is almost impossible to know which antibiotics are being used, and whether they are being used for legitimate veterinary reasons or simply in order to chemically induce animals to grow faster. “I don’t care if you’re a vet or a doctor,” he says. “If we wanted to be in the health business we would take preventive measures. As a society, we need to think of investigating keeping populations healthy and resilient rather than responding after sickness has occurred.”

Dr. David Patrick, an infectious disease physician and epidemiologist who holds posts as director of the UBC School of Population and Public Health and as medical epidemiology lead for antimicrobial resistance at the B.C. Centre for Disease Control, sees the CIPARS data on drug resistance in B.C. chicken as “a signal that has to get people in the B.C. poultry industry asking, ‘What’s going on?’

Patrick thinks physicians need to take responsibility for the antibiotic resistance crisis, too: “It’s a bit rich for us as physicians to cast the attention away onto agriculture,” he says. VGH’s Grant agrees. To stanch the rise of drug resistance at the hospital, she has introduced a comprehensive antibiotic control program in which pharmacists track and review prescriptions. In some cases, physicians are asked to justify their prescribing decisions. But she worries that hospital oversight is not enough. With only four veterinarians in B.C. specializing in poultry, it’s easy to see that veterinary control over drug use on chicken farms is inadequate.

“Most of us would like to see veterinary oversight over all agricultural drug use,” Patrick says, “and the usage of Category 1 drugs stopped.” Instead, farmers can employ a plethora of tactics to avoid veterinary supervision — including a notorious loophole that allows them to import and mix their own drugs on site. As for veterinarians, Patrick observes, the long-standing practice by which they earn a wholesale bonus based on the volume of drugs they prescribe is worrying. “There is an economic incentive to write questionable prescriptions.”

Warnings about the demise of the antibiotic era are nothing new. “It is not difficult to make microbes resistant to penicillin,” noted the drug’s inventor, Sir Alexander Fleming, when he accepted the Nobel Prize for his discovery in 1945. “The ignorant man may easily under-dose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant.”

Warnings about veterinary use of antibiotics have similarly resounded for decades. In 1969, a British government report stated that farmyard drug use posed a serious threat to human health. In 1985, Sweden became the first country to forbid antibiotic use in meat production for anything other than treating illnesses under veterinary supervision. Much of Europe followed suit. The drug bans have had little impact on production or profits.

Last December, the Chicken Farmers of Canada announced it would eliminate preventive use of Category 1 antibiotics, including cephalosporins and fluoroquinolones, by mid 2014. (In the U.S., both practices are already banned by federal regulators.) In addition to these steps, the association said veterinary supervision of all drugs that Health Canada has designated medically critical will become mandatory.

But these are industry rules, not government regulations, and the government will not be enforcing them. The Chicken Farmers of Canada will insist on compliance, says Steve Leech, who manages food safety, animal care, and research for the association. “CFC will enforce rules to eliminate the preventive use of Category 1 antibiotics, via its on-farm food safety program, which is mandatory in all 10 provinces.” But the public will have no way of knowing whether that’s being done, he admits. As Leech acknowledges, his industry does not release information on enforcement. So for now, we’ll just have to trust that chicken farmers will put human health first. Maybe it’s a chicken-and-egg thing?

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