The State of
ANTIBIOTICS A STEEP Analysis
About This Document Since their discovery in the 1920s, antibiotics have revolutionized medicine - eradicating previously fatal diseases, improving quality of life globally, and forever changing the agriculture industry. However, now that discoveries of new antibiotics have become few and far between, the world can no longer ignore the limitations of these drugs. The growing dangers of multi-drug resistance are starting to push global leaders to implement new strategies to extend the lifespan of current antibiotics and to promote innovations, prevention strategies and global stewardship. This document captures a brief glimpse into the state of antibiotics today. Findings are organized using a STEEP framework, examining Social, Technological, Economic, Environmental and Political trends. By analyzing these trends, we at Bridgeable hope to uncover potential futures for the state of antibiotics in the world.
ENVIRONMENTAL SOCIAL
ECONOMIC
TECHNOLOGICAL
POLITICAL
Cause and effect of antibiotic resistance Patients often misuse antibiotics Healthcare practices can promote antibiotic resistance Low- and middle-income countries face unique challenges Antibiotic use continues to grow Agricultural practices promote antibiotic resistance The pharmaceutical industry has shifted away from antibiotics research New tools and technologies could enhance adherence and education, and fight resistance Cutting-edge discoveries are poised to redefine anti-infective therapies The political landscape is shifting
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SEPSIS TUBERCULOSIS
PNEUMONIA
ENVIRONMENTAL
GONORRHEA
ENVIRONMENTAL
Cause and effect of antibiotic resistance In nature, when a population of bacteria makes contact with naturally-occurring antibiotics, the bacteria are wiped out. Occasionally however, one or a few bacterial cells acquire a genetic modification that allows them to survive the effects of the antibiotic. They grow and form new populations of bacteria that are resistant to that particular antibiotic. This is a normal process. For over half a century, humans have been using antibiotics to help cure infections. This has created a problem however in that there has and continues to be much abuse and overuse of these antibiotics, accelerating the rate at which 4 \ THE STATE OF ANTIBIOTICS
bacteria acquire antibiotic resistance. Already, healthcare practitioners are encountering bacteria that are highly resistant to antibiotics. These hard to eradicate bacteria can and have led to the reemergence of untreatable forms of various diseases such as pneumonia, gonorrhea, sepsis and tuberculosis. In Latin American hospitals for example, 90% of MRSA encountered is multidrug resistant (Gelband et al., 2015). Without action, some of these bacteria could move from a multidrug-resistant state to an extensively drug-resistant state to the incredibly dangerous pandrug-resistant state, wherein they are resistant to all known antimicrobial agents. Each year, more than 23,000 deaths in the US and 25,000 deaths in Europe can be attributed to antibiotic resistant bacteria (Baym et al., 2016; Gualano
et al., 2014). Additionally, many people in developing countries die every year due to a lack of access to secondline antibiotics, drugs that have now become necessary due to overuse of first-line therapies. These newer antibiotics are more expensive than first-line drugs. While affordable to high-income countries, second-line drugs cross a cost threshold in low- and middle-income countries that make them cost-prohibitive. The emergence of antibiotic resistance is one of the largest global public health threats faced today. Immediate action needs to be taken to prevent the onset of a post-antibiotic age where infections can no longer be treated with antibiotics.
ECONOMIC
20-50%
OF ANTIBIOTICS USE IS INAPPROPRIATE OR SUB-OPTIMAL
SOCIAL
Patients often misuse antibiotics Broad sweeping misunderstanding for how antibiotics work has led to misuse and improper adherence to the drugs. Reports indicate that between 25-36% of people erroneously believe that a cold can be cured with antibiotics and often seek out antibiotic treatment from their doctor (Watkins et al., 2015; Rodrigues et al., 2013). Alternatively, at the sign of illness 32.7% of respondents to an Italian survey reported self-medicating with their own or someone else’s leftover antibiotics (Napolitano et al., 2015). This practice of using leftover antibiotics occurs around the world. Where do these leftovers
come from? 11.3% of respondents to a survey reported not finishing their last antibiotics course as prescribed, largely because they started feeling better (Cliodna et al., 2007). Many people also believe that the more they take of a particular antibiotic, the likelier their body is to become resistant to its effect, which is not how antibiotic resistance works. It is not an individual problem. It is a community problem. These behaviors and attitudes which promote antibiotic resistance highlight deep misconceptions of how antibiotics work. At the same time, the threat that antibiotic resistance poses is also underestimated; from most patients’ perspectives bacterial infections are very easily treated with antibiotics. As can be seen with the rapid emergence of resistant bacteria, this is not always
going to be the case. Education is an important area to focus on if trying to improve antibiotic adherence. Having health care professionals and antibiotics packaging explain the importance of adherence and the correct uses for antibiotics are two key areas where improvements to patient education can be made. This cannot happen without an attitudinal shift; we need to move away from treating antibiotics as dispensable medications, and instead think of them as a non-renewable resource.
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SOCIAL
54%
SOCIAL
Healthcare practices can promote antibiotic resistance Various pressures lead healthcare professionals to unintentionally make decisions that promote antibiotic resistance. Occasionally, physicians misdiagnose a disease, leading to an incorrect or unnecessary antibiotic prescription. Societal expectations influence prescribing behavior as well. One report found that 54% of physicians believe that patients coming in with a cold are seeking antibiotics but only 26% of patients reported actually coming in seeking these drugs (Watkins et al., 2015). Thus, some physicians prescribe antibiotics for 6 \ THE STATE OF ANTIBIOTICS
colds and other non-bacterial illnesses, in part due to a wrong supposition that it will appease the patient. Issues with treatment protocols also promote antibiotic resistance. For example, due to technical limitations many severe illnesses are currently treated by giving the patient a batch of broad-spectrum antibiotics in the hopes of wiping out whatever mystery bacteria is present. Multiple bacterial populations are targeted at once, increasing the likelihood that one of them will become resistant. Continued healthcare professional training with regards to antibiotics use as well as developments in packaging and infection diagnosis technology could go a long way in preventing improper and non-optimal use of antibiotics.
OF PHYSICIANS THINK YOU WANT ANTIBIOTICS BUT ONLY 26% DO
OVER-THECOUNTER
INFECTION CONTROL
Low- and middleincome countries face unique challenges Around the world, chronic misuse of antibiotics occurs in low- and middle-income countries (LMICs). One issue is that in countries such as Vietnam and Ethiopia, antibiotics can be acquired over-the-counter or through questionable supply chains, allowing for the unfettered use of drugs whose access should be limited. Another issue is that many of these countries do not have proper infection control strategies (e.g. chlorination of water, proper sanitation). The result is that these countries experience a higher frequency of preventable infections which ultimately require much larger
quantities of antibiotics to treat. Proper infection controls sometimes also include the use of antibiotics. In countries such as the United States for example, it’s common practice to administer antibiotics pre-surgery to prevent surgery-acquired infections. In low- and middle-income countries, such practices do not necessarily exist, meaning even larger doses of antibiotics are required post-surgery to treat whatever infection might have been acquired. New policies brought about by global antibiotic stewardship initiatives could prove fruitful in readjusting how antibiotics are used in low- and middle-income countries. Countries such as South Africa, India and Mozambique are already working towards such solutions (see sidebar).
NEW SOLUTIONS IN LMICs In addition to recently developing national action plans to guide future anti-resistance initiatives, the following countries are already taking progressive approaches in the fight against bacteria: South Africa Developed antibiotic surveillance program to profile local and regional resistance patterns. India Placed 24 antibiotics under new category making these illegal to sell without a prescription. Mozambique One of the first sub-Saharan countries to start using vaccines to prevent bacterial infections.
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PREVENT INFECTIONS PROMOTE GROWTH
ECONOMIC
TREAT INFECTIONS
ECONOMIC
Antibiotic use continues to grow Agriculture, a practice that has become dependent on antibiotic use, is a huge economic force driving global growth. This growth necessitates increased use of antibiotics. In 2010, it is estimated that 63,200 tons of antibiotics were consumed by livestock. This number is projected to increase to 105,600 tons by 2030 (Gelband et al., 2015). Healthcare has also seen a similar rise in antibiotic usage. Between 2010 and 2011, worldwide sales of antibiotics for human use increased by 36% (Laxminarayan, 2014).
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Agricultural practices promote antibiotic resistance 80% of antibiotics sold in the US are used in agriculture. These antibiotics serve three main purposes (Gelband et al., 2015): »» To treat infections. »» To prevent infections. »» To promote growth. The promotion of growth is controversial. Farmers will continuously add antibiotics to animal feed to stimulate their growth. This process dramatically increases the amount of antibiotics in the environment and leads to the development of multidrug-resistant antibiotics.
On multiple occasions, antibiotic resistant bacteria in animals have been found to spread to humans. The agricultural landscape is however undergoing some promising change. There is currently a European Union-wide ban on the agricultural use of antibiotics for growth promotion. Denmark, an earlier adopter of a similar policy, has reported no adverse effects to productivity following the ban. Meanwhile, in the United States, the FDA is pushing to fully ban over-the-counter sales of antibiotics for veterinary use.
SHORT LIFESPANS
‘LOW-HANGING FRUITS’ GONE
SHORT PRESCRIPTIONS
LOW AFFORDABILITY
CONSERVATIVE USAGE
The pharmaceutical industry has shifted away from antibiotics research Even with increasing demand, most pharmaceutical companies have retracted from the antibiotics field due to a lack of commercial incentives: »» All ‘low hanging fruit’ antibiotics have been discovered. Discovery of new antibiotics requires considerable investment with low probability of success. »» Prescriptions of antibiotics are for short, low profit courses. »» Due to the quick acquisition of resistance, antibiotics have short lifespans.
»» Newly developed antibiotics need to be conservatively used to slow down the development of resistance. »» Low- and middle-income countries cannot afford expensive second-line antibiotics. Profiting from antibiotics cannot be as simple as selling as much product as possible. This approach is harmful to the environment, and ultimately bad for business. In recent years, UK pharmaceutical companies have aligned to compel the UK government to adopt one of many novel antibiotic business models that would make new research into antibiotics much more attractive (see sidebar).
NOVEL BUSINESS MODELS FOR SELLING ANTIBIOTICS Payer licenses Pharmaceutical companies charge a fixed annual license fee to allow healthcare providers to access to their antibiotics. Value-based model When a new antibiotic is developed, pharmaceutical companies receive direct payments from the government in exchange for pricing this new antibiotic at cost. Patent buy-out The government makes generous purchases of patents for new antibiotics and becomes responsible for distribution.
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TECHNOLOGICAL
CASE STUDY: ClearRx System • Intuitive, clear labeling • Color-coding rings to differentiate each family member • Attached info card with important personal and drug information
TECHNOLOGICAL
New tools and technologies could enhance adherence and education, and fight resistance Tools that promote adherence will be invaluable in the fight against resistance and technologies that promote education and ease of use should be investigated as avenues to accomplish this. When it comes to education, creating antibiotics packaging that uses different communication techniques to help the user learn about proper antibiotic use might help them use the drugs more appropriately (e.g. a sticker that changes
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color when the medication expires). To improve ease of use, changing an antibiotic formulation from multiple doses per day to one dose per day could have a large impact in helping an individual maintain adherence. Another solution would be the successful development of transdermal patches to deliver antibiotics through the skin. These would allow patients to easily stick them on and forget about them until the full course is complete. Another area where new technologies could help fight resistance relates to the way doses are currently administered. In some regions, a patient might require 15 doses of a drug for example yet the drug might only come in 20 dose packs. That leaves 5 doses of antibiotic that
SCREENING TECHNIQUES
likely remain in the patient’s medicine cabinet or go into the garbage and make their way into the environment. Modifications to current packaging practices could resolve this issue. Treatment protocols for severe infections whose underlying bacteria cannot be quickly identified are also problematic. Currently, these infections are treated with overly broad multi-spectrum approaches. Faster pathogen screening techniques and mathematical models of bacterial growth could make identifying pathogens, choosing appropriate antibiotics and calculating necessary dosages easier. This would allow treatments to be more precisely targeted and conservatively administered.
Cutting-edge discoveries are poised to redefine antiinfective therapies Antibiotics are not the only tools that can be used to treat bacterial infections. There is currently much research into identifying new compounds that can replace aging antibiotics. While some of these won’t be commercially viable for many years, others are already making their way through clinical trials.
THE OLD Antibiotics »» Small molecules that kill or prevent bacteria from growing. THE NEW Antibodies »» Big molecules designed to attack the toxins produced by bacteria, effectively disarming them. Some anti-infective antibodies are currently undergoing Phase III clinical trials. Bacteriophages »» Viruses engineered to kill antibiotic-resistant bacteria. Nanotechnology »» Tiny nanoparticles that destroy bacteria by physically ripping open their cell walls.
New research is also shedding light on techniques that can be used to breathe new life into old antibiotics: Two antibiotics working together »» Pairs of antibiotics co-administered at very specific concentrations. Some specific concentrations actually decrease a bacteria’s ability to acquire resistance. Combining an antibiotic with resistance fighters »» Antibiotics co-administered with molecules called Antibiotic Resistance Breakers, can prevent bacteria from using their resistance mechanisms.
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POLITICAL
LIMITED NEW FUNDING
RESTRICTIONS
EXCLUSIVITY
BANS
POLITICAL
The political landscape is shifting Political powers around the world have awakened to the realization that there needs to be a strong worldwide response to the global issue of antibiotic resistance. With the creation of initiatives such as the Global Action Plan on Antimicrobial Resistance, political powers are aligning through global stewardship to develop new holistic policies to combat antibiotic resistance. All corners of the world are getting involved, from the drafting of the Jaipur Declaration in South-East Asia, to the establishment of the ReAct project in Sweden. New policies focus on improving 12 \ THE STATE OF ANTIBIOTICS
sanitation and hospital infection control measures, promoting preventative strategies such as vaccine use and changing public attitudes through education. Some policies are stern such as the European-Union wide ban on antibiotic use for animal growth. Others are more lenient such as the FDA’s recommendation that pharmaceutical companies remove the ‘use of antimicrobial drugs for production purposes’ indication from agricultural antibiotic labels. Fighting resistance also requires new innovations from pharmaceutical and public research organizations which currently only have access to a slow trickle of new funding. This funding is not enough to motivate pharmaceutical companies to commit to high risk anti-infective projects. The situation is slowly changing however. The Biomedical
Advanced Research and Development Authority for example recently promised to provide AstraZeneca with almost $170 million to help them maintain their antibiotics research (Servick, 2015). The FDA’s new GAIN Act also promises to help by providing pharmaceutical companies incentives such as added exclusivity and priority FDA review for antibiotics that target specific pathogens. In the public sphere, the National Institute for Health and the Center for Disease Control and Prevention have recently received generous grants for antibiotics research. The consensus in the anti-infectives field however is that even more needs to be done to incentivize further research and development.
Advancing The Anti-Infectives Field The anti-infective-related issues identified in this analysis are complex, multi-faceted and broad-reaching. While new drug innovations will certainly play a role in helping to stabilize the current antibiotics crisis, there is a growing realization that antibiotic resistance cannot be countered using this approach alone. Sustainable positive transformation will require changing attitudes of many stakeholders, reassessing current business models, adapting to new political realities, and developing unconventional resistance-fighting tools and technologies. In short, to drive meaningful improvements, the problem needs to be tackled holistically, viewing all moving parts as components in this complex ecosystem. Moreover, by adopting a service design approach, it may be possible to identify specific touchpoints and behavior-shifting interventions that collectively can drive broader change within this ecosystem.
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Baym, M., Stone, L.K. and Kishony, R. (2016) Multidrug evolutionary strategies to reverse antibiotic resistance. Science, 351, 40. Gelband, H., Miller-Petrie, M., Pant, S. Gandra, S., Levinson, J., Barter, D., White, A. and Laxminarayan, R. (2015) The State of the World’s Antibiotics 2015. Washington DC: The Center for Disease Dynamics, Economics & Policy. Gualano, M.R., Gili R., Scaioli G., Bert, F. and Siliquini, R. (2014) General population’s knowledge and attitudes about antibiotics: a systematic review and meta-analysis. Pharmacoepidemiology and Drug Safety, 24, 2-10. Laxminarayan, R. (2014) Antibiotic effectiveness: Balancing conservation against innovation. Science, 345, 1299-1301. McNulty, C.A.M., Boyle, P., Nichols, T., Clappison, P. and Davey, P. (2007) The public’s attitudes to and compliance with antibiotics. Journal of Antimicrobial Chemotherapy, 60, i63-i68. Napolitano, F., Izzo, M.T., Giuseppe, G.D. and Angelillo, I.F. (2013) Public Knowledge, Attitudes, and Experiences Regarding the Use of Antibiotics in Italy. PLOS One, 8, 1-6. Rodrigues, A.T., Roque, F., Falcão, A., Figueiras, A. and Herdeiro, M.T. (2013) Understanding physician antibiotic prescribing behaviour: a systematic review of qualitative studies. International Journal of Antimicrobial Agents, 41, 203-212. Servick, K. (2015) BARDA broadens pharma funding to fight superbugs. Science Online, http://www. sciencemag.org/news/2015/09/barda-broadens-pharma-funding-fight-superbugs. Watkins, L.K.F., Sanchez, G.V., Albert, A.P., Roberts, R.M. and Hicks, L.A. (2015) Knowledge and Attitudes Regarding Antibiotic Use Among Adult Consumers, Adult Hispanic Consumers, and Healthcare Providers - United States, 2012-2013. Atlanta: The Centers for Disease Control and Prevention. 14 \ THE STATE OF ANTIBIOTICS
About Bridgeable Bridgeable is a strategic design firm based in Toronto, Canada. Our multi-disciplinary team of designers, strategists and researchers uses service design techniques to understand the world and create multi-faceted solutions that improve people’s lives. We design customer experiences that help organizations create a holistic experience for the people they serve; we design capabilities to help make organizational change practical and real; and we design communications to help clarify complexity.
Contact: Michelle McCune T: 647.888.0053 E: michellem@bridgeable.com