The following is part one in a two-part series examining the use of antibiotics in farm animals and potential threats to human health. This part focuses on U.S. legislative actions, animal antibiotics sales and effects on people. The second part will look at the global and environmental implications, as well as what other countries have done to curb antibiotic-resistant bacteria.

The rise of drug-resistant bacteria is prompting greater scrutiny of animal antibiotics developers and U.S. farmers overseeing food-producing animals that have historically been fed antibiotics as growth promoters.

Antibiotic-resistant infections are responsible for at least 2 million illnesses and 23,000 deaths each year, the U.S. Centers for Disease Control and Prevention said. And antibiotic resistance is projected to kill more people than cancer does by 2050, economist Jim O'Neill reported in 2014.

As recently as Nov. 5, 164 people in the U.S. were reported to have multidrug-resistant salmonella infections linked to raw turkey products, according to the CDC. The investigation is still ongoing, and the outbreak is considered active. An October case of salmonella outbreak stemming from raw chicken products, also still active, additionally involved antibiotic-resistant bacteria. Whole genome sequencing showed that the salmonella bacteria in infected individuals and food and environmental samples were resistant to up to 13 antibiotics, including tetracycline and ampicillin.

The surge in resistance can perhaps be blamed, in part, on overuse by humans. In the U.S., approximately 30% of antibiotics, or 47 million prescriptions, are provided unnecessarily by doctors and other healthcare professionals, the CDC reported. But decades-old farming practices also play a role, according to experts.

Farmers in the 1940s discovered that antibiotics helped food-producing animals grow more and at faster rates, resulting in lower production costs and greater supplies of meat. According to microbiologist Madhab Chattopadhyay, pigs supplemented with antibiotics require 10% to 15% less feed to achieve a desired level of growth. Furthermore, animals fed antibiotics show 1% to 10% improved growth compared to animals which are not fed antibiotics. Antibiotics-fed animals also showed higher levels of protein and less fat, according to a 2002 research paper on antibiotics growth promoters.

Antibiotic-resistant bacteria in farm animals were studied in 1976 by Tufts University biologist Stuart Levy, demonstrating a clear link between antibiotic growth promoters and antibiotic-resistant bacteria, as well as possible transference to humans.

Despite early evidence, it was not until 2015 that the U.S. Food and Drug Administration published a final rule, the Veterinary Feed Directive, mandating veterinary oversight of medicated animal feed, one of the most widespread areas of antibiotics use in farm animals.

Restrictions ushered in by the FDA have centered on medically important antibiotics, which can treat humans in addition to animals and are also known as shared-class antibiotics. However, the majority of restrictions have been labeled as Guidance for Industry, non-binding recommendations left to food producers' voluntary discretion, and much of the remaining regulation is left up to the states. And, though the Veterinary Feed Directive is a federal regulation, veterinarian and executive director of the D.C. Veterinary Medical Association Gail Hansen said the FDA's rule is barely enforced, if at all.

Veterinary and medical professionals, as well as environmental and agricultural professionals, called antimicrobial resistance policy in the U.S. a "complete failure" in a 2016 discussion paper titled "Antibiotic Resistance in Humans and Animals."

The U.S. sold and distributed almost 14 million kilograms of antibiotics for food-producing animals in 2016, according to FDA data. The vast majority — 72% — of all medically important antibiotics used were delivered through animal feed, while 23% were delivered via water.

The 2016 data report from the FDA shows a 10% decrease in antibiotics sales and distribution, measured by kilograms of active ingredient, in the U.S. compared with 2015; however, sales and distribution have increased overall, growing 11% from 2009 to 2016.

Linking antibiotics in farm animals to resistance

Antibiotics use in farm animals, even at low levels, has been proven to be directly linked to antibiotic resistance.

Levy’s 1976 study looked at 150 chickens who had never received antibiotics in their feed. Researchers fed the chickens low doses of the antibiotic tetracycline and found that almost all the E. coli bacteria in their intestines became tetracycline-resistant within one week.

After three months, the bacteria developed resistance to four other types of antibiotics; and in four months, chickens who had not been fed the antibiotic but were at the same farm had tetracycline-resistant bacteria.

The resistant bacteria even jumped to the humans at the farm, with 36% of the farm owners showing tetracycline-resistance, versus 6% in their neighbors.

While health professionals and scientists now know to look for antibiotic resistance in known bacteria like E. coli, salmonella and other gastrointestinal bacteria found in humans, antibiotic resistance is prevalent in bacteria exclusive to animals as well, which is an area that needs more research.

But bacteria can pass on antibiotic-resistant genes through plasmids, DNA molecules separate from chromosomal DNA. Plasmids are able to maintain multiple antibiotic-resistant genes once just one antibiotic gene is selected, due to the genes being linked. Furthermore, plasmids can be shared among bacteria of different species in a horizontal gene transfer. Some bacteria can become resistant to all known antibiotics, according to Tufts University, producing "superbugs."

Multiple studies have since independently sought to study antibiotic resistance and antibiotic use in specific farm animal species and retail products, but the FDA's allowance for animal antibiotics data collection is still limited to a gross total. As such, there is no way to officially break down antibiotics use by farm animal species. For example, farmed fish do not have their own category in the data report.

In addition, the data collection does not account for dosing levels given to farm animals and does not monitor antibiotics use per farm, either.

Part of the limited oversight is due to industry lobbying; the National Chicken Council spent $640,000 in 2014 to lobby on antibiotic-related legislation. The Animal Health Institute doled out $120,000 in 2018 to lobby against similar issues concerning antibiotic resistance.

Pharmaceutical companies have also gotten involved. Eli Lilly and Co., whose animal health unit Elanco Animal Health Inc. was spun out earlier this year as an independent company, documented $150,000 in 2018 and $200,000 in 2017 in lobbying expenditures for Elanco. Lobbied issues included antibiotics restrictions and food safety. Zoetis Inc., the largest animal health company, spent $460,000 lobbying on bills related to animal antibiotics so far in 2018.

Merck & Co. Inc. spent $45,000 in 2018 and $90,000 in 2017 on lobbying for its animal health unit, which also develops antibiotics for farm animals.

Chattopadhyay, the microbiologist, wrote in Frontiers in Microbiology in 2014 that proponents for antibiotic growth promoters "remain unconvinced about the potential of the practice to aggravate the problem of antibiotic resistance," perhaps because of the low doses used in medicated feed compared to doses used for therapeutic purposes. Those who acknowledge antibiotics' impact on antibiotic-resistant bacteria, he wrote, do not believe there is a major effect on human health.

Some food companies are taking action to curb antibiotic use. McDonald's Corp., for example, released antibiotics guidelines Dec. 11 for its top 10 beef-sourcing countries.

Currently, the U.S. Department of Agriculture searches for different chemicals in eggs, poultry and meat, including antibiotics, under the National Residue Program. However, Hansen pointed out, due to the prevalence of antibiotics used at lower levels as growth promoters, those residual substances likely would not be detected by the USDA.

For example, researchers in 2014 found that five out of 47 antibiotics were detectable in U.S. purchased shrimp, salmon, trout and tilapia despite complying with FDA regulations. One antibiotic, virginiamycin, was detected in farmed salmon marketed as antibiotic-free.

As it stands, the prevalence of antibiotics in farm animals poses a great risk to the effectiveness of antibiotics overall, Hansen said.

"If we lose the use of antibiotics, so many things we take for granted won't happen anymore," Hansen said. "Transplants, chemotherapy, hip replacements — if you don't have antibiotics, those could be very risky things to deal with in ways they haven't been for the last 50 years or so, and I don't want to go back to that time."