July 29, 2015
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1. Journal of Law, Medicine, and Ethics current issue on Antibiotic Resistance features proposals from ARC members
The Journal of Law, Medicine, and Ethics has recently released its Summer 2015 issue, dedicated to “Antibiotic Resistance”. The journal includes a number of articles from international experts, spanning across subjects including historical perspectives as well as proposals to address antimicrobial resistance (AMR) at the local, regional, national, and international level.

In the piece entitled “Universal Access to Effective Antibiotics is Essential for Tackling Antibiotic Resistance”, Otto Cars of ReAct Europe along with Nils Daulaire, Abhay Bang, Goran Tomson, and Joan N. Kalyango write that ensuring appropriate, universal access to antimicrobial drugs is critical to achieving the “right to health” as enshrined in various international agreements and organizations including the World Health Organization (WHO). To realize this, they call for collective global action across specific areas including: developing ubiquitous treatment protocols, establishing an international framework and regulations, tailoring interventions to community needs and realities, ensuring effective access to providers trained in standardized regimens, assuring access to affordable antimicrobials, and setting up monitoring and surveillance data systems.

Peter Maybarduk of Public Citizen, another ARC member organization, and Aidan Hollis of Incentives for Global Health also contributed a piece entitled “
Antibiotic Resistance Is a Tragedy of the Commons That Necessitates Global Cooperation” to this special edition. Here the authors frame antibiotic resistance as a “tragedy of the commons” as the rise in antibiotic resistant organisms has diminished the effectiveness of drugs in treating future infections, decreasing the long-term value of these antimicrobial treatments. Furthermore, this is only worsened by the misuse of these drugs. National governments are developing policies to address this issue within their borders, but are often ignoring the externalities imposed on other countries with the costs of resistance being both local and global. The authors call for an international agreement to address the equally important issues of conservation and innovation in order to properly address these issues that have profound impacts at the global level. 

In another piece (“An Integrated Systems Approach is Needed to Ensure the Sustainability of Antibiotic Effectiveness for Both Humans and Animals”), ARC members from ReAct North America (Anthony D. So, Tejen A. Shah), Institute for Agriculture and Trade Policy (Steven A. Roach), and Third World Network (Yoke Chee Ling), as well as Keeve E. Nachman from the Center for a Livable Future at Johns Hopkins Bloomberg School of Public Health called for a One Health approach in combating AMR.

Specifically, they call for an integrated approach across disciplines that addresses the contribution of antimicrobials in food animals to drug resistance and human infection. The authors propose an international agreement as a vehicle to enable a framework for global coordination. They further lay out guiding principles for such a framework including allowing countries flexibility in implementing requirements due to variations in development and local context as well as minimizing disruption of food supplies and livelihoods of farmers by tying transition period milestones to the availability of such support. The international agreement would also serve as an overarching One Health umbrella to integrate surveillance data collection, monitoring and enforcement, research, technical assistance, and financing across countries. The authors conclude that such an agreement would allow for much-needed global coordination to overcome the barriers that domestic measures alone cannot overcome to combat the spread of AMR.
2. Despite White House concerns about legislation, the United States House of Representatives Passes 21st Century Cures Act
On July 10, 2015, the United States House of Representatives approved the 21st Century Cures Act (H.R. 6) by a vote of 344-77, with 230 bipartisan cosponsors. The legislation contains provisions regarding a number of healthcare priorities including promoting the development of novel drugs and devices and expediting their regulatory approval.
The bill also contains specific provisions regarding regulatory and reimbursement incentives for antibiotics including allowing for preclinical data such as animal or laboratory studies, smaller or shorter clinical trials, mathematical modeling, and surrogate endpoints to be considered sufficient evidence for FDA approval. The bill also includes provisions to increase the budget for the National Institutes of Health (NIH) in addition to creating an NIH Innovation Fund of $2 billion annually for five years. Numerous physicians and consumer advocates have written on 21st Century Cures in academic journals and other media, concerned that the bill would further undermine FDA’s regulatory authority and role in ensuring safe and effective drugs and devices through the approval process. 

Prior to the vote, the White House released a statement weighing in on the legislation on July 8, 2015. In this, they commended Congress in crafting legislation that supports President Obama’s Precision Medicine Initiative; the initiative would allow for research towards the development of new biomedical tools and therapies tailored to the needs of individual patients. The Administration, however, also expressed its concern on various parts of the bill, notably providing additional funding to the NIH and FDA without addressing sequestration (the automatic spending cuts put in place a few years ago when the federal government failed to achieve a balanced budget); undermining current regulatory standards and allowing for unsafe and ineffective drugs and devices to be marketed to payors; and extending monopoly drug pricing for certain drugs. The Senate has yet to release a companion bill to the 21st Century Cures Act, but the Senate Health, Energy, Labor, and Pensions Committee is currently working to draft this legislation.
3. Community for Open Antimicrobial Drug Discovery Launches Crowdsourcing Global Initiative
In March 2015, researchers at the University of Queensland Institute for Molecular Bioscience launched the Community for Open Antimicrobial Drug Discovery (CO-ADD). CO-ADD is a non-profit, crowdsourcing global initiative whose aim is to combat antimicrobial resistance by screening donated compounds from academic research groups for potential new therapies. These compounds will be screened at no cost against a specific panel of drug-resistant bacterial and fungal pathogens. If the results of the screening are positive, the academic research group can choose to lead the development of a new therapy with CO-ADD and utilize their resources. Research groups which donate the samples will retain all intellectual property rights to the compound and will be able to file patents or pursue grants based on initial screening results. Researchers, however, must agree to allow for the screening data to be included in a public database 18 months after receiving results. CO-ADD has already received samples from research groups in Australia, New Zealand, India, France and the United States. While the current focus of the project is screening to find new antibiotics, the founders hope to expand it further to other diseases in the future. CO-ADD is funded by the University of Queensland and the Wellcome Trust, which supported a successful, one-year pilot of this initiative. 
4. The CDC finds that antibiotic resistance in foodborne pathogens continues to be an ongoing threat
The Centers for Disease Control and Prevention (CDC) published its 2013 National Antimicrobial Resistance Monitoring System (NARMS) Report on June 9, 2015. NARMS, which tracks changes in antibiotic resistance of common foodborne bacterial pathogens, found that resistance continues to be an ongoing public health threat after testing more than 5,000 microbial samples compared against the previous year’s data.
NARMS is a coordinated effort among state and local public health departments, CDC, FDA, and the United States Department of Agriculture (USDA). More specifically, NARMS also found that multidrug resistance in Salmonella generally remained stable and continued to account for 10 percent of infections. The report also found a linkage between human disease due to a specific serotype of Salmonella and animal exposure as well as pork and beef consumption. Additionally, the report found that for Campylobacter jejuni, the most common bacterial species isolated from humans, one in four samples from ill people were resistant to quinolones including ciprofloxacin. On the other hand, Salmonella resistance to ceftriaxone and quinolones continued to remain rare. In response to the NARMS findings, the White House has requested additional funding for the CDC in the Fiscal Year 2016 Presidential Budget to improve tracking and early detection of drug-resistant Salmonella as well as other antibiotic resistance threats.
5. The European Medicines Agency hosts a first-ever meeting on bacteriophages - a novel therapy to combat AMR
On June 8, 2015, the European Medicines Agency (EMA) convened a workshop on the therapeutic use of bacteriophages - viruses that target bacteria, leaving human cells unharmed. The workshop was attended by various stakeholders including academics, policy makers, patient organizations and industry representatives. While this was the first-ever European workshop on this therapy, bacteriophage therapy has been used by healthcare professionals for decades since the 1920s. Although these medicines have been used extensively, bacteriophage therapy has not been formally approved as a medical product by a regulatory agency. Additionally, no clinical trials have been conducted with phage therapy. Only just this month has the first major multi-center clinical trial across European countries begun funded by the European Commission, specifically targeting infections in burn patients.

The EMA workshop participants discussed the available scientific evidence as well as the potential therapeutic indications for bacteriophage products. Clinicians with experience using these treatments spoke of the need to develop phage therapies targeting specific pathogens. Industry representatives, on the other hand, voiced their concerns around formulating “fixed phage cocktails” to be used in clinical trials. Most participants, however, stressed the need for alternative therapies to currently available antibiotics to address antimicrobial resistance. The EMA concluded that they would continue discussions with stakeholders on the scientific and regulatory aspects of bacteriophages. The United States National Institute of Allergy and Infectious Diseases will convene a meeting this month on these therapies as well. In March 2014, the agency identified phage therapy as one the seven key areas for development in combatting antibiotic resistance.
6. International experts from industry and academia launch Antibiotic Discovery Global Network
Last month, representatives from academia and industry came together to launch the Antibiotic Discovery Global (ADG) Network, an international coalition aimed to address the dearth of new antibiotic compounds in the development pipeline. The non-profit network is free to join and based on the establishment of Antibiotic Discovery UK, a UK-based initiative of industry representatives academics from across 15 manufacturers and 15 universities focused on antibiotic drug development.
The ADG Network will provide a knowledge base of international experts to provide solutions on global antimicrobial development including repurposing older antibiotics for new indications. Besides this, ADG has also stated its support for a Global Antimicrobial Resistance Innovation Fund as proposed in the May 2015 report from the United Kingdom Antimicrobial Resistance (UK AMR) Review. The network will also advocate for the establishment of global Ph.D. and Fellowship programs focused on antibiotic discovery. Finally, besides drug development, the group will also dedicate efforts towards stewardship and prevention measures, including promoting hand washing and curbing the use of antibiotics in animal feed.
Other Recent Developments on AMR
John Oliver calls on US Congress to pass bill protecting poultry farmers from industry abuse
In a May 2015 episode of Last Week Tonight, John Oliver called on the audience to take action to protect contract poultry farmers from industry retaliation. The segment focused on contract poultry farmers and the abuses they experience by the poultry industry, leaving many of them below the poverty line. According to Oliver, almost all chicken grown for food in the United States is produced on these contract farms. Growers are forced to take on huge financial risk including taking out loans to secure facilities and equipment to house chickens in order to secure a contract with poultry companies, which own and distribute the chickens. Besides facing unfair market conditions, farmers can also face retaliation from the poultry industry should they decide to speak out about these abusive practices. In interview clips featured in the segment, farmers retold stories of industry cutting their pay per pound or punishing them by supplying lower quality chickens when they spoke out against the industry.

In fact, the USDA as part of the 2008 Farm Bill created the Grain Inspection, Packers and Stockyards Administration or GIPSA Rule with specific criteria for these contracts in an effort to level the playing field between the farmers and industry. These rules, however, are not enforced thanks to a rider provision introduced into the Agricultural Appropriations Bill by Congressman Steve Womack (R-AR), whose district is home to Tyson Foods, one of the largest poultry companies and a campaign donor. Representative Marcy Kaptur (D-OH), however, had introduced an amendment that would protect the First Amendment Rights of farmers and allow them to speak out against these industry abuses as well as ensure enforcement of the USDA GIPSA Rule. At the end of the segment, Oliver invited the audience to contact their representatives to support these amendments. She had introduced this same legislation in prior years, but it had failed to pass committee. This year, however, the House of Representatives Appropriations Committee voted in favor of this amendment by a vote of 31-18 on July 8. The bill will now continue onto the entire House of Representatives for a vote.
Chinese researchers find high levels of antibiotics in the country’s waterways
Researchers from the Chinese Academy of Sciences recently published results from a study that mapped the antibiotic concentrations in China’s waterways. They examined 58 river basins and found that several of these had very high concentration of antibiotics, primarily near large urban centers including Beijing, Tianjin, and along the Pearl River Delta. The source of these high drug levels traces to human and animal excretion. The study also found that China has now become the world’s largest consumer of antibiotics both in animals and humans; in 2013, total consumption added up to 162,000 tons with animal consumption accounting for 52 percent and human consumption accounting for the rest. Moreover, the results also showed a linkage between bacterial resistance rates and environmental concentrations of antibiotics as well as antibiotic usage. The study published in Environmental Science and Technology is one of the first extensive studies of antibiotic resistance in China. 
SumOfUs and Changing Markets publish report linking pharmaceutical company waste and antibiotic resistance
In a new report, SumOfUs.org and Changing Markets uncovered a linkage between antimicrobial resistance (AMR) and environmental waste from multinational pharmaceutical companies including Pfizer and Teva. Specifically, environmental pollution contributing to this threat comes from the start of the antibiotic supply chain during the production of raw materials. China and India are the world’s largest manufacturers of antibiotic drugs, with China producing over 80% of antibiotic active pharmaceutical ingredients (APIs). These APIs are usually then sold to Western drug companies. Although the pharmaceutical industry has stated that antibiotic manufacturing does not contribute to AMR significantly, the report found that this is actually not true. Instead, investigations and desk research led to the discovery of direct links between major pharmaceutical companies and specific Chinese antibiotic API manufacturers found to have been polluting, thereby further exacerbating the rise of AMR.

The report puts forth specific recommendations on this issue including:
  • Greater transparency of the pharmaceutical supply chain
  • Cessation of procuring antibiotic APIs from polluting Chinese factories and others without strict environmental controls
  • Expansion of existing production standards such as Good Manufacturing Practices (GMP) to include environmental protection criteria
The report is also complemented by an individual sign-on petition demanding that global pharmaceutical companies commit to not purchase products from factories lacking strict environmental controls. The petition also calls for companies to ensure transparency across their supply chain. 
ReAct Latin America signs onto founding statement of the “Union of Concerned Scientists with the Society and the Nature of America Latina”
Last month, ReAct Latin America joined numerous other Latin American organizations at a meeting that established the Union of Concerned Scientists with the Society and Nature of America Latina (UCSSNAL) at the University of Rosario in Argentina. At this meeting, various groups across Latin American signed onto UCSSNAL’s founding statement, which outlined the new organization’s purpose as well as specific commitments and proposals. In this statement, UCCSNAL generally questions the role of science and technology in the current “global civilization crisis” that has worsened socioeconomic inequality and created environmental imbalances. With respect to antibiotic resistance, UCCSNAL has “committed to investigate the global phenomenon of bacterial resistance to antibiotics from the perspective of the social and environmental health”. The scientific organization also committed “to generate tools to allow for community participation and to implement comprehensive solutions to restore the health of ecosystems and promote equity.”
Researchers find that cost-sharing of drugs is significantly associated with antibiotic resistance in low- and middle-income countries
Researchers from the Stanford University, Gandhi Medical College, and the National Bureau of Economic Research published a published a new study in The Lancet: Infectious Diseases earlier this month. The purpose of the study was to assess whether public sector copayments exacerbated antibiotic resistance by incentivizing patients to purchase therapies from poorly regulated private providers. They found that the only factor significantly associated with antimicrobial resistance was out-of-pocket health expenditures, with the positive association driven by countries in which copayments were required under public health plans. Using data from the World Health Organization (WHO) 2014 Antibacterial Resistance Global Surveillance report, the researchers used regression analysis to determine the effect of out-of-pocket spending and copayment requirements for public sector drugs on the proportion of resistant bacterial isolates in 47 low-income and middle-income countries. They controlled for environmental factors that served as predictors of resistance including sanitation, poverty, animal husbandry, and other healthcare infrastructure variables. The researchers conclude that these results suggest that cost-sharing of drugs in the public sector might drive demand into a poorly regulated, informal private sector leading to overprescribing and lower quality of therapies.
Every Woman Every Child posts video of AMR Briefing held last month at the United Nations
On June 15th, Every Woman Every Child of the United Nations (UN) Secretary-General’s Office organized a UN briefing on Antimicrobial Resistance (AMR): An Emerging Global Threat for member states and intergovernmental agencies in New York City. Ten member states co-hosted the event as well as the UN Foreign Policy and Global Health group and the AMR Review commissioned by the United Kingdom. UK Ambassador to the UN, Matthew Rycroft, and Nana Kuo of Every Woman Every Child opened this first of a potential series of events to raise awareness over antimicrobial resistance. Lord Jim O'Neill, Chairman of the United Kingdom AMR Review, as well as Professor Anthony So of ReAct's Strategic Policy Program among others gave interventions on the bottlenecks of antibiotic R&D and potential solutions to address AMR. The stream of the entire event webcast can be found online, alongside a compilation of starter resources on antimicrobial resistance assembled by ReAct North America specifically for this meeting.

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.