June 30, 2016
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AMR on the International Agenda

1. Experts discuss AMR at UN Briefing
2. OIE presents strategy to fight AMR
3. European Council defines next steps to combat antimicrobial resistance
4. G7 makes further commitments on AMR
5. AMR discussed at EAT Stockholm Food Forum

Colistin Resistance

6. Colistin resistance found in human patient and pigs in US
7. European Medicines Agency sets hard targets for reduction of colistin use in animals

Funding Opportunities on AMR

8. GARD receives seed funding for new antibiotic development
9. EU accepting applications for Health Award for NGOs working on AMR
10. White House announces $121 million National Microbiome Initiative

The Antibiotic Innovation Pipeline

11. Pew Charitable Trusts antibiotic development tracker reports 37 antibiotics currently under development
12. DRIVE-AB holds conference on incentives for promoting antibiotic innovation and access

1. Experts discuss AMR at UN Briefing

Watch video coverage of the UN briefing on AMR. →
On June 6th, ReAct-Action on Antibiotic Resistance in collaboration with the Every Woman Every Child initiative within the office of the United Nations (UN) Secretary-General and the Dag Hammarskjold Foundation hosted a briefing on “Meeting the Multisectoral Challenge of Antimicrobial Resistance”. The briefing aimed to raise the issue of antimicrobial resistance or AMR to the top of the political and global agenda in anticipation of a high-level meeting on this issue during the UN General Assembly in September. Here, speakers and participants spoke of the impact of AMR across sectors including human health, agriculture, and the environment. The event, co-sponsored by the country missions of Sweden, Netherlands, South Africa, Vietnam, Mexico, Argentina, and South Korea, brought together a broad range of stakeholders, from high-level government representatives and intergovernmental organizations to private sector and civil society representatives in human and animal health.

The urgency for global coordination to address this growing threat across sectors has never been greater. As Nano Kuo, Manager of Every Woman Every Child, stated in her opening remarks, “Simply put, antimicrobial resistance is one of the most significant global challenges we face today...We will need to galvanize action from across sectors and multi-stakeholders, from the public and private sectors, scientists, doctors, patients and consumers themselves and across the multilateral system. It is clear AMR is not an issue that can be dealt with in isolation.” At this briefing, Lord Jim O’Neill, Commercial Secretary to the Treasury and Chairman of the United Kingdom Review on AMR (UK Review on AMR), gave an overview of the 10 recommendations detailed in the their final report, released in May 2016. These recommendations, spanning across human and animal health, call on Member States as well as other stakeholders including intergovernmental agencies, industry, and civil society to play a part. Dr. Anthony So, Director of the Johns Hopkins Center for a Livable Future and the Strategic Policy Program of ReAct-Action on Antibiotic Resistance, then opened the panel session of the briefing, which included leading figures across both human and animal health from governments, academia, and civil society. Speakers included: Following this multisectoral set of speakers, Dr. Anthony So invited discussants Dame Sally Davies, Chief Medical Officer for the United Kingdom and Dr. Keiji Fukuda, WHO Assistant Director-General and Special Representative on AMR, to offer their reflections. Participants at the briefing were then invited to deliver interventions from the floor. Remarks were given by a broad range of stakeholders including from country mission representatives, intergovernmental agencies, civil society, and the private sector.

Be sure to read our full summary on the United Nations briefing on "Meeting the Multisectoral Challenge of Antimicrobial Resistance" held on June 6th.

2. OIE presents strategy to fight AMR

OIEThe World Organization for Animal Health (OIE) presented its AMR strategy during its General Session of the World Assembly of OIE Delegates on May 24. In line with the WHO Global Action Plan, OIE will ramp up its activities in developing and harmonizing standards for legislation, prudent use, and surveillance; training and education of animal health professionals; resistance surveillance and data collection of antimicrobial use; ensuring the availability of quality veterinary antimicrobials; awareness-raising and communication; and good governance and capacity building. According to an OIE study, more than 110 of the 130 countries surveyed lack legislation regulating the import, manufacture, distribution, and use of veterinary medicines including antimicrobials.
Harmonization and intergovernmental standards. OIE has adopted standards within its Terrestrial Animal Health Code (chapter 1.1.6, 3.4, and chapters 6.7 through 6.10), Aquatic Animal Health Code (chapter 6), and Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. These codes provide recommended frameworks for risk analysis, and surveillance and monitoring. Between 2009 and 2015, the World Assembly of OIE Delegates updated its List of Antimicrobials of Veterinary Importance.

It is worth noting that within the OIE List of Antimicrobials of Veterinary Importance, colistin is categorized as a "Highly Important Antimicrobial Agent." This is an intermediate category above "Important," but below "Critically Important" in terms of importance of conservation. In contrast, WHO classified colistin as a critically important antibiotic for humans as of 2011 due to rising rates of multi-resistant Gram negative infections treatable only with colistin. In general, WHO classifies antibiotics as critically important when there are few therapeutic alternatives to the antibiotic, and when the antibiotic is used for a disease that is either transmitted by or can acquire resistance genes from non-human sources. OIE's category for antimicrobials critically important for veterinary medicine currently includes aminoglycosides, amphenicols, cephalosporins, macrolides, penicillins, fluoroquinolones, sulfonamides, and tetracyclines. WHO considers all of these antibiotics as Critically Important for human medicine except for sulfonamides and tetracyclines, which are rated as Highly Important. The OIE developed their three importance categories based on two criteria. The first criterion is whether more than 50 percent of OIE delegates identified the antimicrobial as important, based on an OIE questionnaire conducted in 2005 (which received 66 replies). The second criterion is whether an antimicrobial has been identified to be essential against specific infections without sufficient therapeutic alternatives. Critically Important Antimicrobial Agents satisfy both criteria, and Highly Important Antimicrobial Agents satisfy only one of the two criteria. By OIE's determination, colistin satisfied the first criterion with 64% of the 66 countries rating it as important, but not the second criterion.

Training and education. OIE updated its guidelines on veterinary education standards to teach veterinarians and para-professionals to conduct appropriate recordkeeping of antimicrobial use and to understand the mechanisms of AMR. OIE recommends legislative frameworks that empower veterinary bodies to oversee degrees, ethics, professional excellence, and the "exclusion of those whose conduct is inappropriate."

Surveillance of resistance and data collection on antimicrobial use. OIE is working to develop surveillance capacity so that consumption and resistance data may guide risk analysis and evaluation of stewardship efforts. The OIE standard on harmonization of surveillance and monitoring programs provides a basis for laboratory-based surveillance of resistant pathogens. Given the gaps in global data on veterinary antimicrobial use, OIE initiated a global survey that will feed into a global database. As of April 2016, 127 out of 180 member states have provided data, while 90 out of those 127 have provided quantitative data. This indicates that many countries have initiated data collection programs, but additional support may be needed to improve national data collection systems. The aim of the database is to enhance traceability of veterinary products, information on imports, and understanding of use trends over time.

Availability of good quality veterinary medicinal products. OIE has stressed the importance of national regulations over the whole veterinary medicine value chain, from development and trade to retail and use. OIE supports wider harmonization of registration requirements by expanding the Veterinary International Conference on Harmonization (VICH), which began as a trilateral program among EU, Japan, and the US. VICH is jointly governed by public sector and industry groups from the three countries. Australia/New Zealand, Canada, and South Africa are "observers" to the VICH process, also with representatives from government and industry. OIE is an "associate member", and the secretariat is the International Federation for Animal Health, a veterinary pharmaceutical industry group. A 2012 study found that among the countries with legislation on veterinary medicines, 22% did not include quality control provisions. To address this, OIE plans to work with relevant international organizations to control the trade of falsified and counterfeit drugs. To reduce the use of antibiotics, OIE is encouraging research on vaccines and alternatives to antibiotics. OIE will host its second International Symposium on Alternatives to Antibiotics, organized by USDA, on December 13-15, 2016 at the OIE Headquarters in Paris.

Awareness and communication, good governance and capacity building. OIE will continue raising awareness, such as through hosting conferences and creating open-access materials for World Antibiotic Awareness Week. To improve governance of veterinary medicines, OIE created the "Tool for the Evaluation of Performance of Veterinary Services" that enables countries to assess their ability to manage risk, level of implementation of OIE guidelines, and areas for improvement. OIE has also requested that member states appoint national focal points for key topics, including AMR, who give expert advice to the national permanent Delegate to OIE. During the current training of focal points, OIE conducts a workshop about data collection on antimicrobial use.

3. European Council defines next steps to combat antimicrobial resistance

European CommissionThe Council of the European Union has laid out next steps for member states and the EU to address AMR. The Council is calling upon member states to adopt national action plans by mid-2017 with a One Health approach and measurable goals to reduce infections, antimicrobial use, and AMR in humans and animals. The Council is also calling for an updated European Action Plan that embodies these goals with provisions for regional coordination and monitoring.

Stewardship. The Council has stated that member state national action plans should include reduction of AMR risk and strengthening prudent use of veterinary antimicrobials, including avoiding routine preventive use. The Council also calls for restricting the veterinary use of antimicrobials that are critically important to human health, such as only allowing use after susceptibility testing. Plans should also aim to reduce AMR risk and strengthen prudent use in human medicine through improved prescribing practices and rational use of critically important antimicrobials. The Council is also calling for improved infection prevention and control, biosecurity measures to reduce infection pressure, and further use of diagnostics.

Innovation. Recognizing the need for new antibiotics, alternative therapies, and rapid diagnostics, the Council highlighted the important role of DRIVE-AB (Driving Reinvestment in R&D and Responsible Antibiotic Use), the UK Review on AMR, and the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). To this end, the Council recommends "dialogue with the pharmaceutical industry" to keep existing effective antimicrobials for humans and animals on the market, while exploring alternative solutions to ensure the availability of these antimicrobials. The Council advises EU-wide alignment of the agendas of existing R&D initiatives and implementation of new business models that include delinkage provisions.

Surveillance. The Council recommends that national action plans include mechanisms for implementation, enforcement, and monitoring. This includes strengthening surveillance to improve the quality and comparability of data reported to ECDC (European Centers for Disease Control and Prevention), EFSA (European Food Safety Authority), and EMA (European Medicines Agency) in humans, animals, the food chain, and "possibly the environment." The Council calls upon the EC to create a harmonized approach to prevent the emergence and spread of resistant pathogens that pose significant public health risks within the food system, such as carbapenem resistance.

Regional and global cooperation. The Council recommends that member states raise awareness among consumers, animal keepers, and relevant professionals. Member states are expected to share best practices and discuss policy options within the EU One Health Network. The EU One Health Network was kicked off in February 2016, and will continue to function through joint meetings of existing EU groups working on human and veterinary health, and the food system. The Council also suggests that countries join or strengthen commitments to the Joint Programming Initiative on AMR. The Council calls upon the European Commission (EC) to assist member states with their national action plans and monitoring systems, including financial support. The Council has requested that the EU develop an updated EU Action Plan on Antimicrobial Resistance (which was originally published in 2011). The Council suggests that this EU Action Plan contain EU-wide measures to prevent infections and ensure prudent use of antimicrobials, combat illegal practices related to the trade and use of antimicrobials (these illegal practices are not specified). The EU Action Plan should align surveillance across humans, food, animals, and environment. The Council has advised the European Commission to promote these EU standards and policies regarding infection prevention and prudent use on the international stage.

Monitoring and evaluation. Over the course of the EU Action Plan's implementation, the Council plans to set goals to reduce AMR prevalence including healthcare associated infections, and decrease differences between member states in the use of antimicrobials. The Council also calls for the development of indicators to evaluate progress on addressing AMR and implementing the EU Action Plan. To increase accountability, the Council has proposed the creation of a voluntary country-to-country peer review system for member states to evaluate national action plans. Such a tool would complement assessment tools from the ECDC Directorate on Health and Food Audits and Analysis, and WHO. The Council additionally calls for annual reports from the EC on activities in implementing the EU Action Plan against AMR and regular meetings of the EU One Health Network on AMR.

4. G7 makes further commitments on AMR

The G7 made commitments on AMR within the Ise-Shima Vision for Global Health following the G7 Summit in Ise-Shima, Japan on May 26-27. These commitments include:
  • Strengthening a One Health approach, including developing integrated surveillance capacity in line with the WHO Global Antimicrobial Resistance Surveillance System (GLASS)
  • Accelerating political commitment through support of the upcoming UN General Assembly meeting on AMR, and of the WHO and countries in implementing national action plans.
  • Preserving antimicrobials as a global public good by regulatory cooperation, information sharing from surveillance and R&D, raising awareness among stakeholders, and phasing out antibiotic growth promoters. The declaration also emphasizes access to safe, effective, and quality-assured antibiotics.
  • Reducing the need of antibiotics by improving infection prevention and control, and access to vaccines, diagnostics, and alternative therapeutics.
  • Promoting R&D for new antibiotics, diagnostics, and other technologies. The document suggests "pull" incentives might be one such way to do so. The G7 will also promote globally harmonized clinical trials and regulatory cooperation to facilitate R&D.
In the leadup to the summit, UK Prime Minister David Cameron urged G7 leaders to contribute to developing new business models that will revitalize the supply of antibiotics. He also called on countries to reduce the demand for antibiotics. He noted that the UK has invested £265 million towards surveillance in developing countries, and £50 million into a global AMR R&D fund. The UK also aims to cut inappropriate prescriptions in half by 2020.

5. AMR discussed at EAT Stockholm Food Forum

Dr. Anthony D. So – Holding food systems accountable
Watch Dr. So's talk at the EAT Stockholm Food Forum. →
On June 13-14, the Stockholm EAT Stockholm Food Forum--where celebrity chefs and entrepreneurs join academics and food system experts--prominently featured antimicrobial resistance. Dr. Anthony So of ReAct’s Strategic Policy Program and Johns Hopkins’ Center for a Livable Future presented on "Holding the Food System Accountable." Dr. So's presentation captured the entwined relationship among climate change, meat consumption and the use of antibiotics in livestock production. One such link he mentioned was a recent study finding that cows treated with antibiotics may emit nearly twice as much methane. These linkages are apparent in China, where meat consumption is rising at a much faster pace than in the US, and producers are moving to an industrial model characterized by increasing reliance on grain imports for animal feed and antibiotic use. The Chinese government has put forth dietary guidelines that recommend people cut their red meat consumption by half, but the question remains of how to translate this normative guidance into reality. Dr. So suggested how AMR might be an entry point into changing the food system, especially since colistin resistance may serve as a "wakeup call for policymakers to take a deeper look at the system of industrial food animal production." He warned, however, that policy interventions can trigger either virtuous or vicious cycles. For instance, an antibiotic tax might might discourage growth promotion use, but a tax might also disproportionately harm smallholder farmers while being too low to deter the use of antibiotic growth promoters by large-scale producers. To enable meaningful monitoring of policy interventions, Dr. So proposed developing approaches that better hold stakeholders accountable. For example, a rapid point-of-use diagnostic could empower communities and consumers to detect resistant pathogens in factory farm runoff or in retail meats.

Dr. John Arne Røttingen, Specialist Director of the Norwegian Institute of Public Health, gave a presentation about the global links among AMR, the food system, sustainable development, and health. He called antibiotics a "wonder drug" that not only treat infections, but also enable complex medical procedures. Therefore, he stressed the need for innovation to increase the supply of antibiotics while also reducing demand through sanitation, infection prevention and control, and improved animal welfare. Dr. Røttingen concluded by highlighting the mutually dependent goals of antibiotic access, conservation, and innovation. This extends to the point that AMR is "a wicked problem" that requires "breaking down silos" among those working within the healthcare system, public health, innovation and manufacture of pharmaceuticals, food production and consumption, and environmental contamination.

The EAT Foundation is a collaborative network for driving interdisciplinary research to reform the global food system. The EAT Foundation was launched in March 2016 with support of the Wellcome Trust, building on the EAT Initiative, which was founded in 2013 by the Stordalen Foundation and Stockholm Resilience Centre.

Colistin Resistance

6. Colistin resistance found in human patient and pigs in US

Bill O'Leary / Washington PostUS Department of Defense researchers at the Walter Reed National Military Medical Center discovered the first documented case of MCR-1 colistin resistance in the US in late May. The colistin-resistant E. coli was found in a 49 year-old woman who on April 26th presented to an outpatient clinic in Pennsylvania with symptoms of a urinary tract infection. Upon receiving the sample, Walter Reed researchers found that the patient's E. coli isolate exhibited not only colistin resistance, but also resistance to 15 other antibiotics, including cephalosporins, fluoroquinolones, sulfonamides, aminoglycosides, and tetracyclines (though not to carbapenems, a last-resort antibiotic class). The patient reported no travel history within the five months before this infection, which indicates a low likelihood that she acquired the resistant pathogen outside of the US. The CDC is now interviewing the patient and reviewing her recent healthcare history to identify how she may have contracted the bacteria. In response to the initial discovery of MCR-1 colistin resistance, Walter Reed began testing all extended-spectrum β-lactamase (ESBL)-producing E. coli isolates being sent to its clinical microbiology laboratory as of May 2016. However, no other human cases have been found yet in the US.

Since late May, two colistin-resistant intestinal bacterial samples from pigs have been reported in slaughterhouses in Illinois and South Carolina. After the detection of MCR-1 in China last November, the USDA Agricultural Research Service initiated a still ongoing study to screen animal samples for colistin resistance. To date, at least 949 animal samples have been exposed to colistin at a concentration that would kill susceptible bacteria while allowing colistin-resistant bacteria to survive. This method has since yielded two detections, the first being on March 3rd, though the finding was not made public until May 26 alongside the Department of Defense report of colistin resistance in the human patient. In one sample, the colistin-resistant E. coli was resistant to other antibiotics including ampicillin, streptomycin, sulfisoxazole, and tetracycline. The second sample of colistin-resistant E. coli was reportedly not resistant to other antibiotics. The USDA has stated it is now conducting traceback work to determine the farms of origin for these samples.

In parallel with the USDA study, the Department of Health and Human Services (HHS) applied whole genome sequencing to scan for colistin resistance in the National Antimicrobial Resistance Monitoring System (NARMS) and National Center for Biotechnology Information databases of 44,000 Salmonella, and 9,000 E. coli and Shigella isolates. Their search did not return any bacteria resistant to colistin. Nonetheless, HHS, USDA, and CDC are reminding consumers to cook meat, poultry, and fish to "proper internal temperature" to kill foodborne pathogens. In addition to retail meat sampling by FDA, NARMS collects post-slaughter food animal bacterial isolates from the USDA Food Safety Inspection Services (FSIS). A recent USDA study has demonstrated that the FSIS sampling methods for Salmonella can lead to false negative results. This is because antimicrobial fluids applied to carcasses post-slaughter can be carried over into test samples, thereby killing pathogens in the sample.

In the US, colistin is approved by the FDA for use in chickens in an injected form. However, Colistin is not listed as one of the drugs "actively marketed" for use in animals in the US according to the FDA's annual reports of antibiotic sales for animal use. Meanwhile, the other antibiotic in its class, polymyxin B, is used for food animal production, and the FDA reports aggregated sales data on its use. Studies have shown that due to the structural similarity of these two polymyxin antibiotics, there is a cross-resistance between colistin and polymyxin B. However, the extent to which agricultural use of polymyxin B might contribute to colistin resistance is an area for further study.

In fall 2016, the CDC Antibiotic Resistance lab network will provide infrastructure and support for 7 to 8 regional labs, and labs in all states and seven major cities to detect AMR threats and conduct real-time reporting. The danger of the emergence of bacteria resistant to all last-line antibiotics was underscored by Lance Price of the Antibiotic Resistance Action Center at George Washington University, "We’re one step closer to carbapenem-resistant and colistin-resistant E. coli  bumping into each other in someone’s gut. It doesn’t matter in which direction the transfer takes place—if the carbapenem-resistant strain picks up colistin resistance, or if the colistin-resistant strain picks up carbapenem resistance. It’s double jeopardy."

7. European Medicines Agency sets hard targets for reduction of colistin use in animals

EMAThe European Medicines Agency (EMA) has updated its advice on the use of colistin in animals to include targets for reduction to be implemented in the next 3 to 4 years. The reduction target for "high consumers" is 5 milligrams per population correction unit (a standardized estimate of animal weight), and 1 mg/PCU or less for "moderate consumers." Based on a review of previous studies, EMA concluded that colistin use is the only demonstrated risk factor for the emergence of colistin-resistant, carbapenemase-producing Enterobacteriaceae. According to the updated advice, possible alternatives may include aminopenicillins, trimethoprim, sulphonamides, tetracyclines, aminoglycosides, cephalosporins, and fluoroquinolones depending on the country resistance situation. These other antibiotics would be used if interventions such as vaccination or improving biosecurity are not undertaken. However, the advice emphasizes that countries go about reducing colistin use without also increasing the use of fluoroquinolones, 3rd and 4th-generation cephalosporins, or antimicrobials overall. There is is variation in use by country, with Denmark using less than 1 mg/PCU whereas Italy and Spain are using 20 to 25 mg/PCU. The advice notes that colistin is of therapeutic importance to treat Gram-negative gastrointestinal infections, especially swine and poultry, and is predominantly administered orally.

The EMA's Antimicrobial Advice ad hoc Expert Group (AMEG) made recommendations endorsed by the Committee for Medicinal Products for Veterinary Use (CVMP) and Committee for Medicinal Products for Human Use (CHMP) that include minimizing sales and moving colistin from Risk Category 1 to the higher Risk Category 2. AMEG classifies Category 1 as antimicrobials whose use is deemed a low risk to public health including penicillins, macrolides, tetracyclines, and polymyxins. Category 2 includes last-line antimicrobials for animals, which overlap with certain classes of antibiotics listed by the WHO as critically important to human health. This category includes fluoroquinolones, 3rd and 4th generation cephalosporins, aminoglycosides, and broad spectrum penicillins. Category 3 includes critically important antibiotics not authorized for use as veterinary medicines. The CVMP recommended the withdrawal of marketing authorization for all products containing colistin in April 2016, but AMEG ultimately disregarded this option due to concerns about potential animal welfare impacts, which could in turn lead to increased use of other critically important antibiotics. AMEG consists of representatives of CVMP, CHMP, European Food Safety Authority (EFSA), and European Centre for Disease Prevention and Control (ECDC).

Funding opportunities on AMR 

8. GARD receives seed funding for new antibiotic development

Brian Simpson / Global Health NowThe Global Antibiotic Research & Development (GARD) Partnership held its official launch on May 24 during the 69th World Health Assembly and announced that it has received seed funding for the development of new antibiotics. Four governments committed to fund GARD - the Federal Ministry of Health of Germany, the Netherlands’ Ministry of Health Welfare and Sports, the South African Medical Research Council, and the United Kingdom Department for International Development. The humanitarian organization Médecins Sans Frontières (Doctors Without Borders) also contributed funding. Together, these five bodies committed €2 million of the projected €3 million needed for GARD's incubation phase. GARD is aiming to finance 3 or 4 projects by the end of 2017, at which point GARD hopes to become an independent operating entity.

This study avoided confounding factors encountered in previous studies by separating out the effect of antibiotics on conjugation efficiency (the rate of conjugation) and on the growth of transconjugants (bacteria with transferred genes). They achieved this by using an engineered conjugation system and experimental conditions where the presence or absence of antibiotics was confirmed to not have significantly changed the growth or death of bacteria. Therefore, the researchers were able to isolate the effect of antibiotics on conjugation efficiency using 10 antibiotics and 9 pathogens.

9. EU accepting applications for Health Award for NGOs working on AMR

The European Commission will present this year's EU Health Award to nongovernmental organizations working to address AMR. Recipients of the award will be added to a European Commission database of best practices in various health fields. Prizes of €20,000,  €15,000, and  €10,000 will be awarded, drawing from funding from the EU's 3rd Health Programme 2014-2020. Shortlisted candidates will be invited to discuss health issues with various stakeholders and the European Commission at the EU Health Policy Web Platform. Applications must submitted by July 31, and any NGO is eligible as long as it is legally registered in the EU Member State.

10. White House announces $121 million National Microbiome Initiative

The AtlanticThe White House Office of Science and Technology Policy announced a new National Microbiome Initiative in May, which will award $121 million to microbiome researchers in Fiscal Year 2016 and 2017. The National Microbiome Initiative aims to increase understanding about how microbiomes maintain the normal functioning of different ecosystems, including in plants, soil, oceans, and within human bodies. Specifically, dysfunctional microbiomes have been associated with obesity, diabetes, and asthma. Microbiome research may provide additional insight on recent findings that link antibiotic use with weight gain in children. The funding sources include the Department of Energy ($10 million), NASA ($12.5 million), NIH ($20 million), NSF ($16 million), and USDA. USDA will contribute $15.9 million for FY 2017 to expand computational capacity for microbiome research through the Agricultural Research Service. USDA has also pledged $8 million to support research, conducted through the National Institute of Food and Agriculture, about the interaction among food production systems and plant, livestock, fish, soil, air, and water microbiomes.

In addition, external organizations have pledged their funding or logistical support. The Bill and Melinda Gates Foundation will invest $100 million over four years towards studies on human and agricultural microbiomes.  JDRF (formerly known as Juvenile Diabetes Research Foundation) will invest $10 million over 5 years to address research related to type 1 diabetes. University of California San Diego is contributing $12 million to its Center for Microbiome Innovation. University of Michigan, with support from the Howard Hughes Medical Institute and Proctor and Gamble, will invest $3.5 million in the Michigan Microbiome Project to provide research experiences for undergraduates. To support open collaboration, One Codex, a company who operates a data platform for microbial genomics, is launching a public portal for microbiome data. BioCollective, a group that collects stool samples for use in research that rewards sample donors with a share of sales revenue, and the Health Ministries Network are investing $250,000 in a microbiome data and sample bank.

The Antibiotic Innovation Pipeline 

11. Pew Charitable Trusts antibiotic development tracker reports thirty-seven antibiotics currently under development

The Pew Charitable Trusts has updated its antibiotic development tracker with information on the 37 new antibiotics in development as of May 2016. Of these 37 antibiotics, 13 are in phase III clinical trials. Historically, 60 percent of drugs entering phase III get approved. At least 11 of the antibiotics have the potential to treat Gram-negative infections, which are particularly difficult to treat and to overcome resistance. This includes three urgent threats identified by the US CDC: drug-resistant gonorrhea, Clostridium difficile, and carbapenem-resistant Enterobacteriaceae. However, of these 11 drugs, only two in novel classes of antibiotics rather than being "me-too" drugs, or drugs derived from existing antibiotic classes or combination therapies using existing antibiotics - BAL30072, a monosulfactam, and POL7080. a macrocycle inhibitor a bacterial outer membrane protein. Of the 34 companies with antibiotics in development, only 5 rank among the top 50 pharmaceutical companies by sales. In fact, small firms are responsible for 80 percent of the products currently under development. Pulling from data provided by Citeline Inc's Pharmaprojects pipeline drug intelligence service and publicly available information from www.clinicaltrials.gov, Pew will continue updating its pipeline tracker twice a year.

12. DRIVE-AB holds conference on incentives for promoting antibiotic innovation and access

DRIVE-ABDRIVE-AB (Driving Reinvestment in R&D and Responsible Antibiotic Use) held a conference on June 2 to formulate concrete policy actions on "Stimulating innovation, sustainable use and global access to antibiotics." The conference brought together 180 experts from pharmaceutical companies, research institutions, WHO, the European Commission, the European Investment Bank, and the US CDC. The conference emphasized the need for global coordination, delinkage of sales volumes from the return on investment (though not necessarily with delinkage of pricing), pilot tests of reward models with support from pharmaceutical companies, and coordinated global public investment in antibiotic R&D to meet public health needs defined by a global body. The preliminary conference report provides a shortlist of incentives for innovation: grants, non-profit antibiotic developers, diagnosis confirmation model, insurance licenses, and market entry rewards. Through continued stakeholder engagement and economic simulation, DRIVE-AB will finalize recommendations on how to prioritize these innovation incentives.

DRIVE-AB evaluated their incentive shortlist according to the type of incentive and innovation stimulated, and rated the incentives according to how likely they would be to promote sustainable use and equitable access.
1. Grants are non-repayable research funds that act as a push mechanism, stimulating early phase research. The shortlist states that grants do not necessarily lead to delinkage, and whether they promote sustainable use, or equitable availability is untested.
2. A non-profit antibiotic developer is an independent organization that creates a push mechanism by managing and financing a portfolio of antibiotic projects through to commercialization. In essence, this represents a Product Development Partnership, similar to ones for neglected diseases.This incentive can stimulate innovation and development with a higher risk profile while also strongly promoting sustainable use and equitable availability.
3. The diagnosis confirmation model is a dual-pricing pull mechanism. A premium price is charged if the antibiotic is used for the entire course. The lower price is charged if it is first used empirically (without confirmed diagnosis) and then de-escalated. This model intends to stimulate a wider range of improved broad and narrow-spectrum antibiotics. The shortlist rates the diagnosis confirmation model as moderately promoting sustainable use by encouraging formulary-driven shifts to cheaper and effective drugs. The model only weakly promotes equitable access.
4. The insurance license model involves governments or private insurers purchasing annual licenses from manufacturers to have access to a specified volume of a particular antibiotic. If a license-holder requires a quantity above the agreed-upon volume, they then pay an additional amount. This is categorized as a pull mechanism that incentivizes development of rarely used emergency antibiotics. Like market entry rewards, insurance licenses guarantee a source of revenue even with low use of the antibiotic, thereby strongly promoting sustainable use but only weakly promote equitable access.
5. Market entry rewards are a pull mechanism with a series of predefined lump-sum payments awarded to the developer after regulatory approval of an antibiotic that meets a pressing public health threat. The shortlist states that market entry rewards would strongly promote sustainable use and equitable availability. Market entry rewards are also at the center of the UK Review on AMR's Final Report and Recommendations.

Other key areas for improvement were also identified, including hospital stewardship programs, infection prevention and control, vaccine coverage, and proper sanitation. DRIVE-AB is a consortium of 16 public sector partners and 7 pharmaceutical companies funded by the European Union Innovative Medicines Initiative (IMI). Half of the IMI's €3.3 billion budget comes from the EU, while the other half comes from the European Federation of Pharmaceutical Industries and Associations (EFPIA) and other life science organizations. This distribution of responsibility is further reflected in the IMI Governing Board, which has 5 members representing the European Commission, and 5 representing industry.

To subscribe to the monthly ARC Newsletter, please sign up here. Visit the ARC website at abrdeclaration.org to view the Newsletter and get other updates on ARC.

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/Strategic Policy Program at Johns Hopkins Bloomberg School of Public Health. 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 rramach9@jhu.edu.