Twilight of Antibiotics?

The outbreak was predictable but still a shock. Salmonella infections emerged in California in March 2013, eventually spreading to 23 states. Although none of the 430 infected victims died, the illness was unusually severe. Nearly 40 percent of those infected required hospitalization. In October, the likely source was traced to people who had consumed Foster Farms chickens. When laboratory analysis discovered that strains causing the infections were resistant to several commonly prescribed antibiotics, the outbreak was seen as another demonstration of the dangers of mass use of antibiotics in industrial food animal production.

Antibiotic resistance has become such a widespread threat that The Lancet Infectious Diseases Commission recently warned: "We are at the dawn of the postantibiotic era." In the U.S. alone, at least 2 million people acquire serious resistant infections every year leading to 23,000 deaths, according to recent CDC estimates. This epidemic of drug resistance is happening as the pipeline of new antibiotics is dwindling.

Since the discovery of penicillin in 1928, antibiotics have heralded a new era in humanity's war against pathogens. They also have been used extensively. An estimated 190 million doses of antibiotics are given to people every year in U.S. hospitals, according to the American College of Physicians (ACP). And up to half of all courses of antibiotics are unnecessary because the patient has a cold or other viral infection, according to ACP.

Misuse of antibiotics in clinical settings plays a role in antibiotic resistance, but the far greater contributor to the problem is the massive use of antibiotics in animal feed, says Ellen Silbergeld, PhD '72, who investigated the issue for 12 years and is writing a book on industrial farm animal production.

Eighty percent of antibiotics produced in the U.S. are used in industrial agriculture, according to the FDA. The sub-therapeutic doses of multiple types of antibiotics given to cattle, swine and chickens are leading to multidrug resistance, says Silbergeld, an Environmental Health Sciences professor. "Scientists who have looked at this issue have concluded that the major contribution to the problem is from animals because of the sheer amounts of antibiotics used in agriculture."

Silbergeld has seen the quantities used firsthand. Told by an FDA official seven years ago that it wasn't possible to buy large quantities of antibiotic feed additives, she went to a feed store on Maryland's Eastern Shore, home to many large poultry-raising operations. When she inquired about purchasing feed additive antibiotics, she was offered several types-in 10-, 25- and 50-pound bags. "I bought 10-pound bags of penicillin and tetracycline. When I tell my clinical friends [this story], they begin to understand the magnitude of the problem."

Robert Lawrence, MD, director of the Bloomberg School's Center for a Livable Future, also finds current practices to be a serious concern. Never "have such large quantities of antibiotics been routinely used at doses destined to accelerate the emergence of resistance," Lawrence says.

Early in his medical career, he says he could never have imagined such antibiotic profligacy. "As new antibiotics were introduced, it was common practice to mandate an infectious disease consultation before releasing the new drug from the hospital pharmacy … to preserve the effectiveness of the new antibiotic as long as possible," Lawrence says.

Yet, the FDA took a different approach when it came to their use in agriculture and began approving antibiotics as additives to animal feeds in 1946, says Silbergeld.

While several countries in Europe have reduced or banned the practice of using antibiotics as growth promoters, U.S. regulators have done little in the last 40 years-only recently adding voluntary guidelines. Public health scientists generally attributed this glacial movement to the combined influence of the agricultural and pharmaceutical lobbies.

Some of their tactics remind Silbergeld of the lead industry in the 1980s challenging public health researchers to "link" lead in gasoline with lead poisoning in a specific child. "When the government actually removed and then banned lead in gasoline," she says, "levels of lead in U.S. children declined in direct proportion to the reduction. Similar findings with respect to antimicrobials and drug resistance have been reported in several EU countries following bans on use in feeds."

Following European bans of antibiotic use in animal feed more than a decade ago, for example, data collected by academic, government and industry scientists in several EU countries showed that rates of antibiotic resistance isolated from bacteria in humans, animals and food items decreased.

The U.S. could learn from the Europeans, Silbergeld says. "We collect such poor data, and industry and government have so successfully resisted legislation to improve data collection, that it is possible for [both government and industry] to continue their claims that absence of evidence is evidence of absence. The other problem is that we don't do anything with the data we do have. This is stupidity in place of science."

Investigators frequently find themselves stymied by industrial producers who deny researchers access to farms and production data, a problem known as the "ag gag." But researchers like Silbergeld have been innovative. She and colleagues Ana Rule, PhD '05, MHS '98, and Sean Evans, a PhD candidate, followed trucks moving poultry to processing plants and detected drug-resistant bacteria on surfaces and in the air inside cars traveling behind trucks carrying broiler chickens. Johns Hopkins PhD candidate Joan Casey (with co-authors Frank Curriero, PhD, MA; Sara E. Cosgrove, MD, MS; Keeve E. Nachman, PhD '06, MHS '01; and Brian S. Schwartz, MD, MS) recently used a large database of health records from a major HMO and plotted the location of patients' homes to show that people with more exposure to large animal operations were at greater risk of methicillin-resistant Staphylococcus aureus (MRSA) infection than those with less exposure. And Silbergeld and colleagues at Johns Hopkins' Homewood campus are seeking grant funding to collect evidence of the history of antibiotic use in Eastern Shore poultry operations by digging core samples of Pocomoke River sediment.

While European countries have already forced the industry to abandon antibiotics as growth promoters, the FDA in the U.S. has yet to require industry to take action. New FDA guidelines released in December 2013 ask pharmaceutical companies to voluntarily revise their labels so that antimicrobial drugs are reserved for disease prevention and treatment under the supervision of a veterinarian rather than growth promotion. The FDA argues that the voluntary guidelines, which include a three-year transition phase, will avoid years of litigation. David Kessler, a former FDA commissioner, told The New York Times: "This is the first significant step in dealing with this important public health concern in 20 years."

To many in public health, however, the voluntary effort seems a weak response. CLF researchers say the new FDA policy will still allow industrial food animal producers to use the same low doses of antibiotics in feeds by simply claiming they are for disease prevention rather than growth promotion.

The new guidelines are not "much of a step forward," says Nachman, a CLF scientist. "Voluntary measures from regulatory agencies are rarely seen as a successful vehicle for making change. I'm glad the agency is paying attention; I'm just saddened that the nature of their attention is not really going to result in a whole lot."