November 21, 2015
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Table of Contents
  1. World Antibiotic Awareness Week: November 16-22, 2015
  2. American Academy of Pediatrics raises concerns about child health impact of antibiotic use in animals
  3. EU proposes to include AMR in Transatlantic Trade and Investment Partnership (T-TIP)
  4. North and South divided in how to approach animal use of antibiotics in the European Union
  5. UK and China start global fund to support collaborative research on AMR
  6. World Organization for Animal Health (OIE) begins development of global database of antimicrobial use for farm animals
  7. Transatlantic Task Force on Antimicrobial Resistance holds meeting to determine future actions
Other Recent Developments in AMR
1. World Antibiotic Awareness Week: November 16-22
November 16-22 marks this year’s World Antibiotic Awareness Week, launched by WHO and observed by several countries and public health organizations that will engage in awareness-raising and sharing of best practices related to the week’s theme of “Antibiotics: Handle with Care.”  The theme aims to build on the WHO’s key objective to improve global understanding about the threat of antimicrobial resistance, as outlined by the WHO Global Action Plan on Antimicrobial Resistance at the Sixty-eighth World Health Assembly this past May.  Specifically, “handle with care” refers to the status of antibiotics as a precious resource which should be conserved and used only with proper oversight from health professionals. The WHO released a campaign toolkit with resources that the general public, health workers, policymakers, and agricultural workers can use to educate themselves and encourage action toward responsible use of antibiotics in humans and animals. The toolkit also provides several online resources including a fact sheet and an online quiz that people can take to test their knowledge about antibiotic resistance.

Earlier this week, the WHO also published a multi-country survey on public understanding of antibiotic resistance. The survey, which includes data from 10,000 people across 12 countries, revealed significant knowledge gaps and misconceptions about antibiotic use and resistance. About two thirds of surveyed people believe that antibiotic resistance is an issue, but most of these people believe that there is nothing that they can personally do to address it. Sixty four percent of people said that medical experts will solve the problem of antimicrobial resistance before it becomes too serious. Further, over three quarters of respondents follow a misconstrued definition of antibiotic resistance; they believe that resistance describes the body building up tolerance to antibiotics, rather than understanding that microbes develop resistance and can then spread resistant infections. The release of these findings is timely, as they can help campaigns like World Antibiotic Awareness Week to target specific knowledge gaps and misunderstandings about antimicrobial resistance and how to address it.

A number of WHO Member States and health partners are hosting local events to raise public awareness about the issue, including the U.S. Centers for Disease Control and Prevention (CDC) and the European Centre for Disease Prevention and Control (ECDC).  ReAct Action on Antibiotic Resistance has organized a variety of events including media conferences, seminars, workshops, radio shows, and a cyclo ride to engage students, children, health professionals, and the general public in learning about appropriate use of antibiotics. These activities span eight countries including Kenya, Zambia, Indonesia, and Thailand. Read more about ReAct Group activities. 
2. American Academy of Pediatrics raises concerns about child health impact of antibiotic use in animals
On November 16, 2015, the American Academy of Pediatrics released a technical report on the link between antibiotic use in livestock and antibiotic resistance in humans, particularly children. The report details the evidence for this link and reviews the mechanisms by which resistant pathogens are transmitted to humans. The report first gives an overview of current data around antimicrobial use in food animals, including recent figures from the U.S. Food and Drug Administration (FDA) that almost 80 percent of antimicrobial drugs sold in the U.S., by volume, in 2012 was for animal use and 60 percent of these drugs are considered medically-important. The authors then detail the mechanism of transmission of pathogens between animals and humans through the food supply. Such transfer of pathogens can occur through either direct exposure to farm workers and consumption of meat with resistant pathogens or through indirect means through wastewaster, fecal matter, and environmental contact. 

The report then delves into the impacts of such exposure on child health. Over 19,000 infections, 4200 hospitalizations, and 80 deaths were reported to the Center for Disease Control and Prevention’s Foodborne Diseases Active Surveillance Network in 2013. The incidence was highest in children under 5 years for most infections. Both U.S. and global policies to limit the use of antimicrobial drugs in agriculture are also discussed in this report including the World Health Organization’s plan for an integrated global surveillance system of livestock. The report also details the recent adoption of FDA’s voluntary guidance to phase out the use of medically important antibiotics from the food animal supply. Based on the evidence linking antibiotic use in food animals and antibiotic resistance in humans, the authors conclude that antibiotic agents should not be used routinely for growth promotion or disease prevention. Instead, they recommend that such agents should only be used to treat and control infectious diseases to prevent further antibiotic resistance and harm to child health.
3. EU proposes to include AMR in Transatlantic Trade and Investment Partnership (T-TIP)
Food Safety NewsOn November 6, the European Commission announced a proposal by the European Union to include an article on antimicrobial resistance within the Sanitary and Phytosanitary Standards (SPS) Chapter of the Transatlantic Trade and Investment Partnership (T-TIP). The SPS chapter outlines regulations for trade of veterinary and animal products, food safety, and animal health. The EU proposed addition of language on reducing the use of antibiotics in animal production and agriculture, citing that “antibiotic resistance is a real global threat to both human and animal health, future food production and food security.” Specifically, the proposed article calls for the creation of a EU-US technical working group with the mandate to exchange best practices, support national systems for AMR surveillance, and develop an antibiotic stewardship program for reduction of antibiotic use in agriculture. This stewardship program would include guidelines to help farmers, veterinarians, and others working with animals to improve animal husbandry practices to avoid unnecessary routine drug use or use of drugs for growth-promotion. The working group would also be tasked with supporting quality assurance programs for evaluation of antibiotic stewardship practices in animal production. 

The EU highlighted the importance of sustainable farming in addressing AMR, stating that the agriculture sector “must preserve the effectiveness of existing veterinary antibiotics” given the difficulty of new antibiotic development. The EU and U.S. are already collaborating on measures to combat AMR as part of the Trans-Atlantic Task Force on Antimicrobial Resistance (TATFAR), which was established at the 2009 U.S.-EU summit. The EU first proposed inclusion of AMR into T-TIP during the October 2015 meeting of TATFAR, but the proposal was tabled for later negotiation between the EU and U.S. The EU views the proposed working group under T-TIP as complementary to the work of TATFAR. 
4. North and South divided in how to approach animal use of antibiotics in the European Union
Despite growing consensus that antibiotic resistance requires urgent multisectoral action, European nations are divided on the formulation of European Commission antibiotic policies for food-producing animals. As reported by Politico, Northern European states and Germany back stricter measures to restrict antibiotics, a view in line with the G7's recent Berlin Declaration. According to the recently published report on European antibiotic consumption in food-producing animals, Southern states like Spain and Italy are among the highest in antibiotic sales. These same countries favor more flexible regulations in antibiotic use in animals. 

Aguilera García, a Spanish Member of the European Parliament (MEP) and rapporteur for the Agriculture and Rural Development committee, drafted a report with suggested amendments to the European Parliament proposal for regulation of medicated animal feed. In particular, García's report proposes to delete language that places a 1% limit on "carry-over" of active antibiotic ingredients between batches of medicated feed during production. Her report argues that these provisions would drive up the costs for medicated feed manufacturers to the point of exiting the market without also leading to concrete AMR reductions. Several members of the European Parliament have criticized García for weakening the Commission proposal on antibiotics. For instance, German MEP Martin Häusling of the Greens/European Free Alliance demanded that certain antibiotics be reserved for human use and called for better documentation on EU drug sales and use. 

Other stakeholders have also expressed the importance of antibiotic innovation and disease prevention. Pharmaceutical companies have argued that the EU should increase funding for developing new antibiotics. Rick Clayton of the International Federation for Animal Health (IFAH-Europe), an organization that represents veterinary medicine manufacturers, argued that funding for antibiotic innovation is important given the expensive R&D process and limited sales and usage. Amanda Cheeseley of Copa-Cogeca, the largest EU farmer organization, agreed that funding new antibiotic development is a "key factor to fight antibiotic resistance." Jan Vaarten from the Federations of Veterinarians stated that "disease prevention is even more important prudent use" instead of restricting or banning antibiotics. A vote on a European Commission proposal to limit the use of antibiotics in animals that are not sick had been postponed from September to November, and it has been delayed again to February 2016. 
5. UK and China start global fund to support collaborative research on AMR
China and the United Kingdom have announced a joint Global Antimicrobial resistance Research Innovation Fund of 9 million pounds to support innovative collaborations between researchers from the two countries. The UK Medical Research Council, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council will contribute 4.5 million pounds through the Newton Fund, an initiative to strengthen research partnerships between the UK and "emerging knowledge economies." The Chinese government will provide matching funds through the National Science Foundation of China. The funding agencies are hosting a workshop on November 24-26, 2015 in Shanghai to increase understanding of the antibiotic research landscape in the two countries. The workshop will refine the fund's four themes, which are:
  1. Research on development of resistance, epidemiology, and transmission dynamics of AMR within and between species
  2. Development of antibiotics and alternative treatment approaches, and understanding the mechanisms of action for antibiotics and alternative therapies currently used in humans and animals. This theme also encompasses research on business models, and economic, social, and behavioral issues surrounding development and use of treatments.
  3. Change in behavior, organizational, and cultural norms and incentives to prevent AMR in human and animal settings.
  4. Understanding the functions and interrelationships among healthcare and veterinary systems, such as how formal systems can draw on local, informal practices. This theme also includes mapping the supply chain and incentive systems for antimicrobials. 
The fund was announced during President Xi Jinping's state visit to the UK this October, and a call for proposals will take place in December 2015.
6. World Organization for Animal Health (OIE) begins development of global database of antimicrobial use for farm animals 
The 180 Member Countries of the World Organization for Animal Health (OIE) committed during their General Assembly last May to support the WHO Global Action Plan on Antimicrobial Resistance. Last month, the OIE released a statement of its plans to develop a global database on antibiotic use and resistance in animals, in alignment with the Global Action Plan’s mandate to improve antimicrobial surveillance worldwide.  The new database will be managed in parallel with the OIE’s World Animal Health Information System (WAHIS), a publicly accessible computer system that collects and reports real-time data on animal diseases. Antibiotic use in food-producing animals will be collected through the national Veterinary Services, and the global database will also be supported by the WHO and Food and Agriculture Organization (FAO).  The OIE noted the importance of the novel database, as there is currently no centralized system for monitoring and reporting of antibiotic resistance worldwide. Furthermore, about 110 of OIE Member Countries still lack legislation regulating the production, distribution, and import of veterinary products like antibiotics. The OIE claims that the database will address these issues by giving countries access to information on the movements and quality of veterinary products, in addition to addressing gaps in knowledge about antimicrobial resistance.

The OIE also recently updated their list of antimicrobial agents of veterinary importance, to be adopted into Member Countries’ legislation in order to better inform national surveillance and risk analysis of the spread of antimicrobial resistance in animals.  The global database and related efforts represent the continuation of a Tripartite Alliance established among the OIE, WHO, and FAO in 2010.  The Alliance’s goals include developing strategies for a One Health approach to address health risks at the animal-human-ecosystem interface of antimicrobial resistance. 
7. Transatlantic Task Force on Antimicrobial Resistance holds meeting to determine future actions
The Transatlantic Task Force on Antimicrobial Resistance (TATFAR) convened in late October to formulate proposals for joint actions in the next five years. These actions will include standardizing the definition of appropriate antibiotic use for surveillance and producing a review of AMR reduction targets. TATFAR will also work to characterize transmission, surveillance, and communication for AMR interventions in veterinary medicine. The meeting also called for further policy dialogues on regulatory control and actions to strengthen surveillance and compliance. In their opening remarks, Vytenis Andriukaitis, the EU Commissioner for Health and Food Safety, and Lydia Mutsch, the Luxembourg Minister of Health, called for global commitments for further collaboration, education, national monitoring programs, and research-enabling environments. Minister Mutsch emphasized supporting international action on AMR, with a focus on new proposals on animal use of antibiotics within the European Parliament. Professor Otto Cars, co-founder of ReAct, led a panel on the second day that began with a session on regulation and stewardship to ensure access to antibiotics while conserving the effectiveness of new ones. Also included were specific workshops on the appropriate therapeutic use of antimicrobial drugs as well as prevention of drug-resistant infections in both human veterinary medicine and also strategies for improving antimicrobial innovation. The meeting concluded with a closed session for TATFAR partners to develop action plans for these goals.
Other Recent Developments in AMR
The Lancet releases series on antimicrobial access and resistance during World Antibiotic Awareness Week
During World Antibiotic Awareness Week, The Lancet published a series entitled “Antimicrobials: access and sustainable effectiveness” on November 18th. The series reframes the challenges of antibiotic access and resistance as issues of sustainability, with a particular focus on targeting policy domains to improve international collaboration on ensuring long-term antibiotic effectiveness. The first two papers in the series focus on the problems and challenges associated with antibiotic access and antimicrobial resistance, while the last three papers examine potential policy intervention points for improving issues of access and sustainability. According to an article authored by the Center for Disease Dynamics and Economic Policy (CDDEP), which delved into both human and animal use of antibiotics, improved access to antibiotics is estimated to prevent the deaths due to pneumonia of greater than 75 percent of children under five each year across 101 countries. Researchers find that instead of using antibiotics to treat pneumonia in this age group, the scale-up of vaccines against pneumococcus and Haemophilus influenzae type b could prevent up to 11.4 million days on antibiotics per year, a 47 percent reduction in 75 countries. This would conserve antibiotics through preventing the development of resistance. Given these findings, they argue for prioritization of antibiotic access for children and neonates. The study also finds that although human antibiotic consumption is increasingly globally, restrictions to access to antibiotics have caused greater mortality than antibiotic resistance. Finally, researchers also project that worldwide antimicrobial consumption will rise by 67 percent in 2030 with the rise in demand for livestock. They also suggest that a ban on antimicrobials used for growth promotion would only to moderate production losses worldwide and that there continues to be a high correlation between antibiotic use and antibiotic resistance in food animals.

Another piece by Christine Årdal of the Norwegian Institute of Public Health and colleagues including Anna Zorzet of ReAct Europe calls for urgent, collective global action against antimicrobial resistance based on current evidence, while recognizing the need for more robust evidence to understand transmission of resistance from animals to humans. Coordinated global collaboration is specifically needed to address antimicrobial resistance across three policy areas - innovation, responsible use, and universal access. These areas must be integrated such that interventions to increase innovation and access to antimicrobial drugs should also include responsible use provisions in order to ensure drug effectiveness and prevent further resistance. The authors also call for delinkage of the payments of these drugs from the volumes sold in order to mitigate inappropriate incentives to waste antimicrobials. Additionally, as the challenge of antimicrobial resistance is multisectoral, spanning across the health, agricultural, and veterinary sectors, global collaboration through a One Health strategy is necessary. The authors call for a combination of “quick wins” and long-term solutions in multiple policy areas - surveillance, universal access, infection prevention and control, responsible use, and innovation. These solutions would also need to be coupled with better global coordination and financing. The authors put forth two possibilities at the intergovernmental level - namely, an international treaty with strong enforcement provisions as well as a UN-level coordinating body. 

Osman Dar of Public Health England and colleagues including Anthony So of ReAct North America and Jasper Littman of ReAct Europe address the challenges of combatting antimicrobial resistance in low- and middle-income countries (LMICs). Moreover, the authors state there is an inadequate evidence base to inform policymakers of the effectiveness including generalizability and cost-effectiveness of antimicrobial policies, specifically in the areas of responsible use, surveillance, and infection control and prevention. The authors examine policies across these three areas, providing assessments of their effectiveness and generalizability. In particular, they find that there is a lack of evidence around cost-effectiveness of interventions such as surveillance and infection control across LMICs. Additionally, within these countries, they also call for a specific focus towards monitoring drug quality and counterfeit drugs. From this examination of antimicrobial resistance policies across different areas, the authors conclude that standardized policy assessments should measure cost-effectiveness and adaptability to the local context with a comprehensive political, regulatory, and technical landscape analysis. The authors also call for a One Health approach that would allow for the development of policies that can be tailored to the sector involved and adaptable to the specific country or regional context. 
Gaps remain in public knowledge about antibiotic resistance
A team of researchers from Queensland, Australia recently published a systematic review of public perceptions and beliefs regarding antibiotic resistance (ABR). The review surveyed 54 studies comprising interviews and questionnaires of 55,225 people from Europe, North America, and Asia. The researchers found that many people (70%) had heard of antibiotic resistance and believed that it was a problem. However, most people (88%) didn’t fully understand how resistance develops and also believed that the ABR threat is not something over which individuals have control or responsibility. Survey participants tended to attribute ABR development to the actions of others and believed that clinicians should take on the full responsibility of decreasing excessive antibiotic use. However, clinicians have a very different view of their role in combatting antibiotic resistance. In another systematic review published this past summer, the same researchers reviewed a combined 57 studies that surveyed 11,593 medical professionals’ perceptions of ABR. While the vast majority of surveyed clinicians believed that ABR is a serious global health problem, less than 70% thought it was a problem related to their own practice. Causal attributions for ABR development also differed from those of the general public. Instead of viewing clinician practices as the main driver of resistance, most of the surveyed health professionals believed that patient non-adherence and excessive antibiotic use were the main culprits. 

Taken together, these findings on public and clinician perceptions of ABR can guide interventions for tackling overuse and misuse in clinical and household settings. The authors noted that their research highlights the need for public education on why antibiotic resistance is “everyone’s problem,” and how “it is individuals who have the power to minimize use and halt antibiotic resistance.” From a clinical standpoint, health professionals have the ability to ensure that patients understand the implications of antibiotic overuse and are aware of available alternatives for common infections. The authors also noted the role that international organizations and policymakers can play in controlling ABR, through improved resistance surveillance, regulating antibiotics in agriculture, infection prevention, and incentivizing innovative drug development. 
Chipotle's faces shortage in US of antibiotic-free meat, turns to UK supplier
Restaurant chain Chipotle has recently faced a shortage of pork produced in the US that meets its "Responsibly Raised" standards that require animals to never receive antibiotics. This shortage comes as a result of a failure to adhere to these standards by one of Chipotle's existing suppliers. For this reason, Chipotle has now begun supplying pork from the UK-based supplier Karro Food, which follows European antibiotic standards that do allow the therapeutic use of antibiotics under veterinary supervision. This stands in contrast with Chipotle's publicly strict policy to source meat from animals raised without antibiotics. The company emphasized, however, that their meat would continue to be free of antibiotic residues since animals treated with antibiotics from Karro would be subject to the withdrawal period mandated both in the US and Europe. As reported by NPR, veterinarian Gail Hansen, who previously worked for the Pew Charitable Trusts, suggested that it is not always feasible never to give antibiotics to animals, and she voiced her approval of Chipotle's transparency about possible therapeutic use by Karro Food. This is not the first shortage in antibiotic-free meat that Chipotle has faced. In 2014, the chain served chicken and beef in which non-therapeutic antibiotics were used in some locations during shortages of antibiotic-free chicken and beef. That year, Chipotle also began sourcing grass-fed beef from Australia because the US supply of antibiotic-free meat could not keep pace with the demand for Chipotle's products.
Noodles & Company makes commitment to remove antibiotics from supply chain by 2017
Noodles & Company, a restaurant chain, announced in early October a commitment to source by 2017 meat and poultry from animals that have never been given antibiotics or hormones. The commitment comes as a part of the chain's rebranding that will also lead to the removal of "artificial colors, flavors, preservatives and sweeteners from its core menu." The company began serving antibiotic-free pulled pork in 2012 and has introduced antibiotic-free bacon this past month. Noodles & Company plans to remove antibiotics from its steak and meatball options by "mid to late 2016" and from chicken by early 2017. Like Chipotle, Noodles & Company is a "fast-casual" restaurant chain with 470 locations in the US.

Note: The ARC Newsletter will periodically capture key meetings and developments, as well as news and resources, on antibiotic resistance for Coalition members and partners. This newsletter is prepared and published through ReAct North America and the Program on Global Health and Technology Access at the Sanford School of Public Policy at Duke University. The ARC Declaration on Antibiotic Resistance can be found here. Please share items for consideration for inclusion in future newsletters by writing to Reshma Ramachandran at reshma.ramachandran@duke.edu.