August 31, 2015
View this email in your browser
1. Antimicrobial resistance highlighted as a Sustainable Development Goal in final UN Draft of 2030 Agenda for Sustainable Development
At the end of July, an official draft of the UN 2030 Agenda for Sustainable Development was released, outlining 17 Sustainable Development Goals (SDGs) and 169 target areas. This agenda, in part, continues where the Millennium Development Goals (MDGs) left off. The document now includes a direct reference to antimicrobial resistance. Under the section, “The new Agenda,” the draft now reads: “We will equally accelerate the pace of progress made in fighting malaria, HIV/AIDS, tuberculosis, hepatitis, Ebola and other communicable diseases and epidemics, including by addressing growing antimicrobial resistance and the problem of unattended diseases affecting developing countries.” The inclusion of AMR within the agenda came as a result of advocacy efforts from organizations including ReAct Europe. The draft of the post-2015 development agenda will go through a final round of intergovernmental negotiations before adoption at the upcoming United Nations Summit during September 25-27 in New York City.
2. Challenges remain in the diagnosis and treatment of diarrhea in children
An article in The New York Times highlights challenges to treating diarrhea in children--a problem that claims the lives of 700,000 infants every year, second only to pneumonia. According to WHO treatment guidelines dating back thirty years, children with diarrhea are to receive rehydration and a zinc supplement. Based on these, antibiotics should only be administered when blood is present in the stool.
Recent studies however, have found that bacterial causes are more common than previously thought and that blood is not always present. The Global Enteric Multicenter Study found that three of the top five causes of childhood diarrhea were in fact, bacterial. Some experts suggest changing the WHO guidelines because many children do not receive antibiotics, and then die or end up stunted by persistent infections. Tarik Jasarevic, a WHO spokesperson, responded that these new studies were "important, but not enough to change guidelines" given the danger of antibiotic resistance. Dr. Anita Zaidi, director for diarrheal diseases at the Gates Foundation, however, believes fears of resistance should not justify withholding antibiotics. She called this issue "a matter of equity", pointing out how travelers receive antibiotics for the same infections.

Given that lab-based diagnosis takes days and involves refrigerating stool samples, resource-limited clinics often rely on the WHO guidelines. Meanwhile, Polymerase Chain Reaction (PCR) testing has allowed for rapid and accurate diagnosis for tuberculosis. Tests like GeneXpert have improved TB diagnosis, but a similar device for the multiple causes of diarrhea has not been developed. Canadian researchers have created "flocked swabs" that pick up DNA from the rectum without a stool sample, but they still require PCR testing. While Dr. Zaidi has advocated for revising the WHO guidelines to allow more antibiotic treatment instead of spending millions to develop on-the-spot PCR tests for diarrhea, concerns over increasing antibiotic resistance persist. The WHO has stated its guidelines may change depending on further research and is now collaborating with the Gates Foundation on a study to see which children would benefit from antibiotics when doctors do not know the cause of illness.
3. Wellcome Trust study finds that UK public misunderstands antibiotic resistance
The Wellcome Trust released results from a study conducted by a consultancy firm, Good Business, which aimed to understand public perceptions of antibiotic drugs and antibiotic resistance. Through a series of interviews and focus groups across the UK, researchers found that most people have misconceptions around antibiotic resistance. A majority of interviewees thought that their bodies became resistant to antibiotics instead of bacteria. The study also found that most people wanted to be prescribed antibiotics regardless of what illness they had, potentially leading to antibiotic overuse. Few responded, however, that they felt like they overused or misused these medicines.
 
Moreover, although resistance was discussed generally in both interviews and focus groups, respondents did not seem to understand the concept of “antimicrobial resistance” or “AMR”. Many participants thought "resistance" referred to the human body building up resistance rather than specific bacterial pathogens becoming resistant against antibiotic drugs. Respondents also believed that a solution to address AMR will be found before it becomes a “real problem” either through new science or increased funding for a “cure.”
 
The study also found that people understood the concept of antimicrobial resistance better when doctors, media, and others spoke about “drug-resistant infections” or “antibiotic-resistant germs” instead of “antibiotic resistance.” Using such terms allowed for respondents to grasp that bacteria acquire resistance, instead of one’s body. Based on these results, researchers speculate that this misconception may be why patients often fail to complete their regimen of antibiotics, thinking that consuming less will prevent their bodies from becoming resistant to the drugs. 
 
Additionally, the study found that language around the economic costs and mortality rates due to antimicrobial resistance used by scientists and in the media to describe the issue made participants feel distanced from the problem and even put off. Instead, interviewees responded more to references to common infections that are becoming increasingly hard to treat due to resistance such as strep throat or urinary tract infections. They also responded more to examples of how antimicrobial resistance could affect them or their families. 

The Wellcome Trust stated that this study’s results are valuable in encouraging doctors and other healthcare professions to make small shifts in language such as using the term “drug-resistant infections” rather than “antibiotic resistance” so that patients can better appreciate the issue and accept medical advice. The work also highlighted the need to make antibiotic resistant infections an issue more personally relevant and important to the individual. Otherwise, as the Director of Strategy at Good Business states, “it just feels like someone else’s problem.”
4. On eve of Subway’s 50th anniversary, NRDC launches U.S. campaign urging public commitment to antibiotic-free meat
On August 26th, the National Resources Defense Council (NRDC) launched a national campaign targeting Subway during the week of its 50th anniversary and asking the world’s largest fast food chain to only purchase meat products raised without the routine use of antibiotic drugs. 
This campaign follows a letter sent in late June to Subway CEO Frederick DeLuca and President Suzanne Greco from NRDC and more than 60 other organizations including Friends of the Earth, Consumers Union, ReAct Europe, and the Johns Hopkins Center for a Livable Future. Both the letter and campaign urged Subway to commit to a three-part plan as follows:
  • Defining a time-bound action plan to phase out any routine use of antibiotics across Subway meat supply chains;
  • Acting immediately to end the routine use of antibiotics important for human medicine in the production of chicken sold in Subway restaurants; and
  • Adopting third-party auditing of its antibiotics use policy implementation and benchmark results to show progress in meeting the goals described above.
NRDC notes in their press release that Subway has been “suspiciously silent on its antibiotic policies” while its competitors including McDonalds, Chick-Fil-A, Panera Bread, and Chipotle have announced that they would phase out routine use of antibiotics by their suppliers. They also state that the use of routine antibiotics in animals to allow them to grow more quickly or survive crowded and unsanitary conditions contributes to spread of drug-resistant bacteria. Despite these changing industry standards and the initial letter, Subway has yet to publicly commit to purchasing antibiotic-free meat or disclose its practices.
 
NRDC has set up a large billboard along the highway corridor near Subway’s headquarters in Milford, Connecticut. The billboard asks if the fast food chain is buying meat produced with antibiotics. NRDC is also inviting individuals to sign onto a petition, directed at Subway leadership, noting that global antibiotic use is expected to rise by 67 percent by 2030, further exacerbating antibiotic resistance worldwide. More information on the campaign can be found at www.nrdc.org/subway.

5. Drugmakers and food industry groups oppose FDA proposal on antibiotic reporting
The Food and Drug Administration (FDA)’s proposed plan requiring veterinary drug manufacturers to report species-specific information on antibiotic use is now facing strong industry opposition. The proposal, released in May 2015, is part of a larger White House strategy to curb antibiotic resistance. Currently, companies are only required to report total sales of individual drugs. This information is released in annual distribution reports mandated under the Animal Drug User Fee Amendments of 2008 (ADUFA). According to the FDA, delineating this data by animal species would allow the agency to better monitor antibiotic use and develop targeted solutions to curb the spread of resistant pathogens. The FDA welcomed comments regarding this rule earlier this month.

Comments submitted by industry state that providing such level of data would be difficult to produce and misleading. The American Feed Industry Association (AFIA) challenged this proposal. They argued that the FDA proposal requiring species-specific data is not supported by current law, since such data is not listed among the reporting requirements in Section 105 of ADUFA. Companies also opposed provisions that would allow FDA to utilize drug use estimates when data are not available. Other groups including the American Veterinary Medical Association cautioned against the use of the data alone in establishing the connection between antibiotic use in certain food animals and resistance as the data may be inaccurate. The National Cattlemen’s Beef Association also commented that drug manufacturers would likely only be able to provide estimates of specific usage and that different production classes within species might receive varying amounts of antibiotics, further obscuring the data.

Other stakeholders countered industry opposition to the proposal. These groups argued that such livestock-specific data would assist researchers in further understanding the connection between antibiotic resistance and use of specific drugs in various types of food animals. Pew Charitable Trusts also noted that the data would likely show a downward trend in the use of antibiotics as several poultry producers have already stopped using these drugs in their food animals. 

The FDA has also worked with pharmaceutical companies to decrease the use of antibiotics on farms and to curb the rise of drug-resistant bacteria. A report released by the FDA in April 2015 showed that the sales of medically important antibiotics for animal use rose 20 percent between 2009 and 2013. Manufacturers have now voluntarily agreed to phase out the use of these drugs for growth promotion in food animals.


At the end of September, the FDA along with the United States Department of Agriculture and the Centers for Disease Prevention and Control will host a meeting to obtain public input on possible data collection methods for farm usage of antibiotic drugs. In April 2015, the USDA laid out specific proposed initiatives for the collection of such data including:
  • longitudinal studies to assess the relationship between antibiotic use and development of resistance;
  • collation of AMR data from veterinary diagnostic laboratories;
  • annual national estimates of antibiotic use in feed or water for feedlot cattle, broilers, swine, and, potentially, turkeys;
  • further refinement of National Animal Health Monitoring System data including analyzing antibiotic use in different varieties of poultry and livestock as well as targeted data collection on specific pathogens;
  • collection of proprietary data from food animal companies on species-specific use of antibiotics.
Public comments regarding this forthcoming interagency plan are being accepted until November 30th.
6. US Senators Continue to Demand that Public Health Experts Have a Seat on Interagency Task Force for Combating Antibiotic Resistance 
As reported on Senator Elizabeth Warren's website, Senators Warren, Dianne Feinstein, and Kirsten Gillibrand sent a letter on August 17, 2015 to the Interagency Task Force for Combating Antibiotic-Resistant Bacteria asking how they would address gaps in FDA policies on the use of antibiotics in food animals. This letter comes as a follow-up to a December 2014 letter that went unanswered; this time, the Senators asked for a response within 30 days.
The letter demands the Department of Health and Human Services appoint at least 3 experts who understand how overuse of antibiotics in animals leads to resistance and do not have a conflicting business interest to the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria. The letter states that industrial animal producer associations and veterinary drug companies have publicly doubted the need to reduce antibiotic use in animals despite concerns from public health experts. The FDA phase-out of agricultural antibiotics allows for disease prevention use; moreover, the phase-out is voluntary and lacks the force of law. Given that 400,000 Americans get antibiotic-resistant foodborne bacterial infections per year, these three Senators are calling for more accountability in food safety regulation.
7. A Consumer Reports study found conventionally-produced ground beef twice as likely to contain multidrug-resistant bacteria compared to sustainable beef
Consumer Reports found that 18% of conventionally produced ground beef contained multidrug-resistant bacteria compared to 9% of sustainably produced ground beef in a sample of 300 packages purchased in different types of stores in 26 cities around the US. While all of the samples contained bacteria indicating fecal contamination, sustainably produced ground beef was less likely to contain S. aureus and E. coli. In their sample, more than 80% of conventional beef contained two types of bacteria, nearly 20% contained C. perfringens - which causes one million food poisoning cases annually in the US, and 10% contained a S. aureus strain that can produce a sickness-inducing toxin that cannot be destroyed even with proper cooking. The sustainable beef came from organic and/or grassfed cows raised without antibiotics, treated more humanely, and given access to pasture. 97% of US beef comes from conventionally raised cows, and 80% is produced by just 4 companies. They finish their lives in feedlots where they are fed antibiotics, hormones, corn, and soy for maximum growth efficiency. The report recommends consumers pay attention to labels and choose beef with "grass-fed," "organic,” and "American Grassfed Association" labels.

Cooking beef to 160 degrees Fahrenheit kills most harmful bacteria. However, 28% of Americans eat raw or undercooked ground beef, according to the CDC. This can increase the potential for getting sick, especially since the grinding process for ground beef can distribute bacteria throughout the meat. Between 2003 and 2012, there were almost 80 outbreaks of E. coli O157 due to contaminated beef, leading to 1,144 infections, 316 hospitalizations, and 5 deaths. The CDC estimates for every E. coli O157 case reported, another 26 go unreported. An estimated 48 million people in the US experience foodborne illness each year, with beef as the number 4 cause. Consumer Reports recommends that USDA and FDA ban regular antibiotic use in healthy animals, ban the "natural" label which does not indicate raising methods or feed, expand welfare standards for organic beef, increase inspections at every meat plant, ban the sale of beef containing antibiotic-resistant pathogenic Salmonella, and prohibit chicken waste in cattle feed. 
Other Recent Developments in AMR
Al Jazeera special showcases experts including ARC founding member on antibiotic resistance
In a special episode of the Cure that focuses on antibiotic resistance, Joff Locey journeys around the world to showcase different parties working on antibiotic resistance. Locey interviews Richard Young, policy director of Sustainable Food Trust and a founding member of ARC. On his farm, Young speaks about how antibiotics used for disease prevention and growth promotion in farm animals is linked to antibiotic resistance for humans.Featured also are Dr. Vanya Gant - Clinical Director for Infection at the University College of London Hospital, Keiji Fukuda - the WHO Assistant Director-General for Health, Security and Environment, Dr. Hazel Barton - a microbiologist at University of Akron who cave-dives in search of new antibiotics, Dr. Jennifer Hughes - a physician who treats multidrug-resistant tuberculosis for Doctors Without Borders, Phumeze Tisile - a survivor of extremely drug-resistant tuberculosis and co-author the Drug Resistant Tuberculosis Manifesto, and Jonathan O'Halloran - founder of QuantuMDx and developer of Q-POC, a promising new rapid diagnostic test. Locey travels through England, Switzerland, the US, and South Africa; he ends with the message that experts around the world are rising to the significant challenge of addressing antibiotic resistance.
Article highlights antibiotics resistance as a collective action problem
An article in The Atlantic compares antibiotic resistance to climate change, as both are problems of collective responsibility - one person's antibiotic consumption could diminish the public good for others. Each year, 700,000 people die from resistant infections, a figure estimated to rise to 10 million by 2050. A 2015 Proceedings of the National Academy of Sciences study found that countries like Russia, Brazil, India, South Africa, and China will likely experience the largest growth in antibiotic resistance, with antimicrobial use in animals estimated to double by 2030. In March, President Barack Obama published the National Action Plan for Combating Antibiotic-Resistant Bacteria, which includes $1.2 billion of federal funding. Laxminarayan called for surveillance and stewardship to prevent inappropriate use, which can arise when antibiotics are given before test results arrive, when broad-spectrum antibiotics are used empirically for bacterial infections that are unknown, or when antibiotic treatment is not reduced in patients after diagnostic tests come back negative. At the individual level, Fauci suggests that patients and physicians should have more conversations about antibiotics, and Laxminarayan recommends eating vegetarian.
Study finds antibiotic resistance can increase bacterial fitness
A study published in Science Translational Medicine provides evidence that the widely held belief that drug-resistant bacteria are less fit is not always true. The study found that antibiotic resistance mutations in 3 different pathogenic bacteria species provide a growth advantage and increased virulence in mice and rabbits. The researchers created a library of engineered mutant bacteria strains, from which they isolated two antibiotic-resistant strains. One of the mutations affects a gene linked to resistance in P. aeruginosa-infected patients, encoding a channel that allows carbapenem antibiotics to enter bacterial cells. Another isolated gene encodes a channel that allows fosfomycin to enter cells. This mutant could also kill macrophages in vitro, which may contribute to its ability to evade attack by a host immune system. These two mutants, and two strains isolated from patients infected with naturally occurring antibiotic-resistant P. aeruginosa, led to lower survival rates for infected mice. This suggests these strains were more virulent compared to antibiotic-sensitive strains. Based on previous studies that show a link between antibiotic resistance and decreased fitness, microbiologists had assumed that stopping the use of antibiotics after treatment course would create selective pressure against resistant bacteria. However, if antibiotic resistance increases fitness in some cases, stopping antibiotics in this way may not effectively reduce resistant bacteria.
Smart wound dressing capable of detecting infections receives accelerator funding
Researchers at the University of Bath have received accelerator funding of £900,000 for a recently developed a "smart wound dressing" that gives rapid visual indication of bacterial infection. As described in the concept paper, fluorescent sensors light up under ultraviolet light in the presence of pathogenic bacteria. Currently, the dressing can identify Pseudomonas aeruginosa and Staphylococcus aureusThe dressing was designed for early detection of toxic shock syndrome (TSS) resulting from burn infections. Left untreated, TSS is especially dangerous for young children. Importantly, this dressing is triggered only by disease-causing bacteria, which could help physicians decide if an antibiotic treatment is necessary. The researchers will use the funding to design, manufacture, and package a final prototype for human trials. Under the eighth round of the Biomedical Catalyst fund, £18 million will be given to twelve promising new treatments, diagnostics and other medical technologies being developed by researchers in the United Kingdom. The fund is run through the Medical Research Council and Innovate UK with the purpose of supporting UK academics and smaller companies attempting to commercialize their research. 
More hospitals adopt UV-disinfecting robot technology
Lima Memorial Health System in Ohio and East Jefferson General Hospital in Louisiana mark the latest customers of Tru-D SmartUVC, a disinfection robot that uses ultraviolet (UV) light to systematically disinfect hospital rooms. Upon sensing the dimensions and contents of a room, the robot calculates the level of UV light to kill viruses, bacteria, and fungi. Evaluations of Tru-D in 2010 and 2013 found that the Tru-D can substantially reduce bacteria populations in hospital rooms, including for Methicillin-resistant Staphylococcus Aureus (MRSA) and Vancomycin-resistant Enterococci. The Tru-D is now used in Canada, the UK, the US, and Saudi Arabia. It was also briefly deployed in Liberia to supplement Ebola disinfection efforts in clinics. UV disinfection technologies show potential in reducing the burden of hospital-borne infections compared to existing methods of cleaning in healthcare settings.
Report Suggests Upward Trend in Recalls of Both Organic and Conventionally Produced Food
As reported in the Stericycle Quarterly Recall Index, recalls of both organic and conventionally produced food have increased in the past year, casting doubt on whether organic food is safer. According to the USDA, 70% of consumers think that food is safer or of higher quality if labeled organic. In the second quarter of 2015, the FDA issued 178 recalls, an increase of 47% over the previous quarter. 62% of these recalls were for bacterial contamination, mostly for salmonella and listeria. Vegetables accounted for 61% of these recalls. USDA recalls also increased in the second quarter of 2015, which amounted to 10.7 million pounds of food, 10 times the volume recalled in the first quarter. 90% of these were due to undeclared allergens. Organic food recalls accounted for 7% of the food recalled, up from 2% in 2014. In 2012 and 2013, just 1% of recalled food was organic. In a New York Times article, Stericycle's Vice President stated that since 2012, all organic food recalls were due to bacterial contamination. Though this may raise concerns about the safety of organic food, the Organic Trade Association points out that these recalls do not necessarily mean organic food is less safe. Rather, the 25% growth of the organic industry and increased food safety mechanisms since 2012 may explain these recalls. for  Stericycle counts units of food, but perhaps it is more reasonable to count number of recalls. Further, an opinion piece in Food Safety News puts forth other limitations to the report, suggesting that recalls at the grocery store level are underreported and that not all recalled food pose immediate health risks. For example, between two organic spinach recalls this year - one for listeria risk and the other for pesticide residues beyond allowable limits - no illnesses have been reported from consumption of products containing this spinach. Therefore, the trends are not yet clear as to how likely organic food is to cause sickness compared to conventionally produced food.

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.