The following is part two in a two-part series examining the use of antibiotics in farm animals and potential threats to human health. This part focuses on the global and environmental implications, as well as what countries outside the U.S. have done to curb antibiotic-resistant bacteria. The first part looked at U.S. legislative actions, animal antibiotics sales and effects on people.
While foodborne illnesses may be the most apparent threat of antibiotic-resistant bacteria manifesting among farm animals, one of the most alarming aspects of the phenomenon is the effect on the surrounding environment.
The United Nations Frontiers 2017 report on Emerging Issues of Environmental Concern pointed out that "bacteria in soil, rivers and seawater can develop resistance through contact with resistant bacteria, antibiotics, and disinfectant agents released by human activity."
Due to the presence of antibiotic-resistant bacteria in animal waste, the germs are then exposed to the surrounding air, and potentially insects and other animals, according to Gail Hansen, a veterinarian and executive director of the D.C. Veterinary Medical Association.
The World Health Organization enacted a global action plan to combat antimicrobial resistance in late 2015, an initiative followed by the U.N. declaring the world's commitment to addressing antimicrobial resistance across sectors in September 2016.
The action plan includes the Global Antimicrobial Resistance Surveillance System, which standardized data collection and analysis, an annual World Antibiotic Awareness Week and partnerships.
Demand for organic meat
Consumer awareness of the issue is rising, according to a 2017 study on retail chicken and turkey brands and antibiotic-resistant E. coli. The study noted that demand for "raised without antibiotics," or RWA, and organic products is increasing as well.
That demand has influenced the companies that manufacture antibiotics for farm animals, such as Zoetis Inc. and Elanco Animal Health Inc. Both Zoetis and Elanco have noticeably pulled back from promoting such products in recent years, according to Evercore ISI analyst Umer Raffat.
Additionally, both companies have joined a framework for antibiotic stewardship in food animal production, to which the National Milk Producers Federation, National Pork Board, National Pork Producers Council and National Turkey Federation have also agreed. The framework, announced on Dec. 18, is a consensus that includes veterinary guidance, preservation of antibiotics, best approaches to treatment and keeping records. According to Pew Charitable Trust, those involved with the framework acknowledge that it is broad, and actual implementation of the principles remains to be seen.
Zoetis' senior director of corporate communications Elinore White emphasized that the company does not permit the use of its medically important antibiotics or feed additives for preventive purposes in the U.S.
"Prevention can be many things to people, but we refer to it as what the government authorities define it as," White said.
She added that getting FDA approval for a preventive indication for an animal antibiotic is difficult.
Zoetis also began an Individual Pig Care program to promote well-being among farm pigs.
Meanwhile, Raffat pointed out in an October note that Elanco's biggest product is Rumensin, a livestock antibiotic administered as a feed additive; Rumensin has accounted for 10% of Elanco's revenue, totaling $270 million. He highlighted Elanco's exposure to medicated feed, which is still "quite large," as a disadvantage, especially when compared to Zoetis.
Elanco stopped promoting medically important antibiotics in August 2016, Raffat wrote — an encouraging development.
Both Zoetis and Elanco highlighted product development in probiotics as a replacement for medicated feed additives during their third-quarter earnings calls.
Denmark's 'yellow card system'
In Europe, similar concerns from public health officials and consumers have put pressure on antibiotics makers. Sales for use in food-producing animals dropped by more than 20% across the EU between 2011 and 2016, according to the European Medicines Agency. Even so, six EU member countries reported increased sales of such products.
Most EU countries that seek to rein in antibiotic resistance have emphasized the importance of setting goals, Hansen said.
For example, the Netherlands told its food animal industry in 2009 that antibiotics usage needed to be cut by half within three years — a goal that was accomplished a year early.
"If you don't set goals, things aren't going to change," she said. "The U.S. hasn't set any goals. One of the reasons is, we're not sure what the right number is, and that's true, but nobody knows what the right number is; just pick a figure and work toward that goal."
Hansen held up Denmark as a positive example. Veterinarians there are required to enter data on how much antibiotic is used for which animals, for how long and for what reasons, into a national database. There is also a "yellow card system," Hansen said, with the power to penalize farms that exceed the antibiotics allowance.
"I don't see that happening in the U.S.," Hansen said. "Denmark is a much smaller and more homogeneous country, and there's political support to develop that database."
The Animal Health Institute, a nonprofit membership organization that represents animal health companies, conducted a case study in 2009 on Denmark's ban in 2000 of antibiotic growth promoters. The study found that death and disease increased among farm animals as a result of a sweeping ban. In addition, "while resistance to some antibiotics has decreased in animals, resistance to other antibiotics has gone up," the institute wrote.
For example, ciprofloxacin-resistant E. coli bacteria in pigs increased to 3% between 1997 and 2004 and decreased to less than 1% in 2009. However, tetracycline resistance increased in salmonella bacteria in poultry, pigs and humans.
The Animal Health Institute hypothesized that a ban on antibiotic growth promoters may cause an increase in disease and mortalities, thus resulting in an increase in antibiotics use for therapeutic purposes.
The National Pork Board, which also studied Denmark's ban and its effects on antibiotics use and resistance, said, "There have been no proven human health benefits from the ban on [antibiotic growth promoters] in pork production."
Furthermore, according to the Animal Health Institute, the chance of humans contracting antibiotic-resistant bacteria from antibiotics-fed animals is extremely low. Citing the Harvard Center for Risk Analysis, the institute said the likelihood of humans acquiring resistant Campylobacter bacteria from macrolide-treated poultry and subsequently experiencing treatment failure is less than 1 in 14 million.
However small, there is still some risk, as an October salmonella outbreak in the U.S. demonstrated. The outbreak occurred after antibiotic-resistant bacteria from food-producing animals were transferred to infected humans.
Moving away from antibiotics
Researchers like Stuart Levy of Tufts University have continued to advocate for limited antibiotics use as growth promoters, and have noted the positive effects of European bans.
A 2011 paper by Levy and Tufts research associate Bonnie Marshall found that there was a decline in antibiotic-resistant bacteria over time following European bans, such as a 1995 ban on avoparcin, which had given rise to vancomycin-resistant Enterococci bacteria, or VRE. According to Levy and Marshall, "a dramatic reduction in human carriage of VRE also followed the ban on avoparcin."
Hansen said the issue is larger than simply reducing antibiotics: Animals need to be raised in cleaner environments.
The shoulder-to-shoulder living conditions of certain farm animals, made famous by the 2008 documentary "Food Inc.," cause animals to be more vulnerable to disease, kicking off a negative feedback loop of greater susceptibility, more widespread antibiotics use and consequent antibiotic-resistant bacteria.
While animal health professionals await the FDA's finalized proposal for measuring additional biomass data and antibiotic application, the 2017 report on antibiotics sales and distribution data — the first year reported since FDA guidance advising against use for growth promotion and feed efficiency was implemented — may provide some hints as to how closely the FDA's guidelines are being followed.
A summary of the report, released Dec. 18, boasted a 33% decline in sales and distribution of all medically important antibiotics between 2016 and 2017. All antibiotics included in the report dropped to sales levels below those of 2009, the first year such data was published, except for two medicines.
However, while these numbers seem to bode well for the state of antimicrobial resistance in the U.S., 62% of medically important antibiotics were administered via feed and 30% were delivered in medicated water. While both are improvements from 2016, the antibiotics administered via water actually went up by 13% compared to 2009.
"While I'm very pleased with the results of the report, and the efforts by all of our stakeholders [including animal pharmaceutical and feed industries] thus far to improve antimicrobial stewardship, our work isn't yet done when it comes to fighting antimicrobial resistance," FDA Commissioner Scott Gottlieb said in a news release on the findings.