The Challenge

The 2018 Innovate4AMR Challenge: Antibiotic Stewardship in Resource-Limited, Healthcare Settings

INTRODUCTION

Antimicrobial resistance (AMR) occurs when microbes develop resistance to the drugs we use to treat infections. With few truly novel classes of antibiotics coming to market, global attention has focused particularly on these antimicrobial drugs that treat bacterial infections. The more antibiotics are used, the greater the risk that bacterial resistance will develop. Antibiotics are the cornerstone of many of the miracles of modern day medicine, from cancer chemotherapy to organ donation. The loss of effective antibiotics would mean reverting back to a time when simple infections might become untreatable. Each year, 700,000 people die due to drug-resistant infections and, if unchecked, this number may rise to 10 million deaths a year by 2050 — more than the number of people that die of cancer today. Antibiotics should, therefore, be considered a resource to be used with care. Yet underuse, overuse and misuse of antibiotics is prevalent in many settings, from hospitals and outpatient clinics to farms.

In 2015, Member States adopted a Global Action Plan on Antimicrobial Resistance at the World Health Assembly, and in 2016, the UN General Assembly took up a global health issue for only the fourth time in history and adopted the UN Political Declaration on AMR. Countries have actively worked to put in place National Action Plans on antimicrobial resistance. However, there remains an urgent need for developing innovative, scalable approaches to address the challenge of conserving existing antibiotics. This is an intersectoral challenge that will demand a society-wide response. However, healthcare professionals have a particularly crucial role to play in bringing attention to the issue, both within the healthcare setting and within their local and global communities.

Innovate4AMR seeks to engage student teams to design novel strategies for key actors that have influence over how antibiotics are used appropriately or not in the healthcare delivery system.

Teams may be composed of up to five students (see eligibility criteria on our website) and are encouraged to draw from interdisciplinary talents. Two members of each winning team would be supported to come to a capacity building workshop in Geneva, Switzerland. Additional members could attend with their own resources. Potential solutions should embrace a theory of change, focus appropriately on the local context, have plausible feasibility and the potential for scale-up and sustainability (both financially and logistically). A visual representation of the key actors and intervention points can be found in the Innovate4AMR educational materials.

In this challenge, we provide a brief overview of the key stakeholders and intervention pathways to ensure improved antimicrobial stewardship in resource-limited settings. As teams consider where to focus their proposed solution approach, we urge you to review closely the range of potential intervention points in the accompanying AMR Stewardship Prezi (linked here). We hope that the Prezi presentation will help inspire you to come up with creative solutions to this pressing global health challenge. We’re counting on you–our future generation of leaders.

HOSPITALS

At the institutional level, hospitals are a key focal point for intervention. In hospital settings, seriously ill patients present, often requiring immediate treatment with broad-spectrum antibiotics before a diagnosis of bacterial infection or drug resistance testing can be completed. Bacterial infections may affect any organ in the human body–e.g., lungs (pneumonia), kidneys and bladder (urinary tract infection), or bloodstream (sepsis). The testing for bacterial infection and whether the infection is resistant to first-line antibiotics used for treatment depends on the hospital having reliable laboratory facilities. Antibiotics used in the hospital setting, unlike most outpatient treatment, may be administered parenterally or intravenously instead of being taken orally. If a bacterial infection is resistant to first-line antibiotics, an alternative or second-line antibiotic regimen may be used. Antibiotics may be used in combination to cover the range of potential infections until a laboratory diagnosis is made.

Challenges can include stockouts of second-line antibiotics to treat drug-resistant infections, unaffordability of antibiotic treatments, the lack of appropriate local treatment guidelines, the lack of adequate microbiology facilities, the failure to provide lab-based, audit-and-feedback to guide clinicians, and difficulties in implementing infection and control procedures such as hand hygiene. Complicating this situation, fewer than two-thirds of hospitals providing surgical care in nineteen LMICs had a reliable source of water.

Background Literature

Various strategies are used to improve hospital antimicrobial stewardship: preauthorization of antibiotic use, formulary restriction, audit and feedback. [Chung GW, Wu JE, Yeo CL, Chan D, Hsu LY. Antimicrobial stewardship: A review of prospective audit and feedback systems and an objective evaluation of outcomes. Virulence 2013; 4(2):151-157. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654615/pdf/viru-4-151.pdf]

The impact of antimicrobial stewardship programs in hospitals might be measured by changes in the use of these drugs and savings in costs, resistance patterns and the incidence of antibiotic-related adverse effects (e.g., Clostridium difficile infection), and hospital length of stay, readmission rates and mortality. [Akpan MR, Ahmad R, Shebl NA, Ashiru-Oredope D. A Review of Quality Measures for Assessing the Impact of Antimicrobial Stewardship Programs in Hospitals. Antibiotics 2016; 5(5):1-16. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810407/pdf/antibiotics-05-00005.pdf ]

Both enablement approaches (defined as “increasing means/reducing barriers to increase capability or opportunity”) and restriction (defined as “using rules to reduce the opportunity to engage in the target behavior) were found to increase compliance with antibiotic policies in hospitals. [Davey P, Marwick CA, Scott CL, Charani E, McNeil K, Brown E, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database of Systematic Reviews 2017;(2):CD003543 doi.org/10.1002/14651858.CD003543.pub4]

Current Efforts

At the same time, the WHO Essential Medicines List recently classified antibiotics according to how widely available or restricted such drugs should be, taking into account the risk of drug resistance. This classification system, called AWaRe, has three categories: Access, Watch and Reserve. Antibiotics in the Access category should be available to all patients in need in all facilities. Watch antibiotics pose a higher risk of resistance and should only be prescribed for specific instances. Reserve antibiotics should only be used as a last-resort when all other treatments fail. How best might one implement this approach in low-resourced settings?

Opportunities for Innovation

–What role might telehealth play in improving antimicrobial stewardship where local infectious disease consultation may not be available?

–How might the strategic use of treatment guidelines and of locally generated antibiograms improve hospital stewardship of antibiotics in resource-limited settings? [Hindler JF, Stelling J. Analysis and Presentation of Cumulative Antibiograms: A New Consensus Guideline from the Clinical and Laboratory Standards Institute. CID 2007;44: 867-873. Available at: https://academic.oup.com/cid/article/44/6/867/364325 ]

–Could innovative financing approaches or cost savings from antimicrobial stewardship programs enable insurers or hospitals to invest in these efforts? [Oberjé, E. J. M., Tanke, M. A. C., & Jeurissen, P. P. T. (2017). Antimicrobial Stewardship Initiatives Throughout Europe: Proven Value for Money. Infect Dis Rep, 9(1), 6800.]

–Are there ways to encourage best practices across a network of hospitals? [The Breakthrough Series: IHI’s Collaborative Model for Achieving Breakthrough Improvement 2003; 1-20.]

–How can hospital accreditation support the adoption of antimicrobial stewardship practices?

 

Outpatient Clinics

In the outpatient clinic setting, patients present to healthcare workers with a range of symptoms. Any of a number of symptoms or signs may suggest a bacterial infection treatable with antibiotics—fever, shaking chills, cough, sore throat, abdominal pain, burning on urination, a wound with drainage. The healthcare provider will have a short window of time to evaluate the patient’s presenting complaint, obtain a history and complete a physical exam, order diagnostic tests, and propose a treatment plan. This treatment may or may not include prescribing an antibiotic. In some resource-limited setting, healthcare workers use clinical algorithms to evaluate, say, a child presenting with fever. To narrow down the possible diagnosis, a rapid diagnostic test might be used, and a positive finding might suggest to the healthcare worker to treat for malaria. The respiratory rate—if too high—might suggest a pneumonia, treatable with oral antibiotics. If more severe, the referral decision might be made to send the patient to a hospital to be further evaluated and admitted for antibiotics that can only be administered intravenously. The approach taken will depend on the local prevalence of bacterial disease, lab infrastructure and training of healthcare workers.

The patient may be a child, brought by a parent who may have taken off work to come to the clinic. The patient or the parents bringing in a child may expect the healthcare provider to offer a prescription, even if the infection is likely viral and not treatable with an antibiotic. Patients may have traveled significant distances to be seen at the clinic. Knowing that the patient might not easily return if the condition worsens, the provider might offer an antibiotic prescription in order to avoid missing a bacterial infection in case the symptoms are not self-limited and worsen. Clinic arrangements may limit the time the provider has with each patient and whether diagnostic tests are available. Financial incentives and drug company promotion can also influence whether healthcare providers prescribe or not.

Challenges include:

• Non-financial incentives, such as patient expectations of antibiotic treatment
• Financial incentives
• Availability (or not) of appropriate, rapid diagnostic tests
• Local pharmacy availability (or stockout) of needed antibiotic
• Opportunity for referral for hospital evaluation
• Feasibility of watchful waiting and delayed prescription
• Institutional constraints, such as short visit time

Background Literature

Making available antibiotic guidance in the practice setting, by signposting to online references and in printed materials. Auditing prescribing activity at the practice level can also help guide steps as to where to position information or training to improve antibiotic stewardship. [Owens R, Jones LF, Moore M, Pilat D, McNulty C. Self-Assessment of Antimicrobial Stewardship in Primary Care: Self-Reported Practice Using the TARGET Primary Care Self-Assessment Tool. Antibiotics (Basel) 2017; 6(3). Available at: https://www.ncbi.nlm.nih.gov/pubmed/28813003 ]

The “Treat Antibiotics Responsibly, Guidance, Education, Tools” (TARGET) toolkit—grounded in the evidence of earlier, successful interventions—engaged prescribers in reflecting on their own practices through a self-assessment questionnaire and local prescribing data, educational resources for both provider and patient (including waiting room materials) audit toolkits and national antibiotic management guidance among other components. [McNulty C, Hawking M, Lecky D, Jones L, Owens R, Charlett A, et al. Effects of primary care antimicrobial stewardship outreach on antibiotic use by general practice staff: pragmatic randomized controlled trial of the TARGET antibiotics workshop. J Antimicrob Chemother 2018; 73(5): 1423-1432. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909634/pdf/dky004.pdf

Current Efforts

Behavioral economic approaches might also usefully shape prescriber behavior. In Australia, the Chief Medical Officer sent letters to high prescribers among general practitioners. The letters that provided comparisons to their peers had more effect than the education-only message. [Australian Department of Health and Department of the Prime Minister and Cabinet. Nudge vs Superbugs: A behavioural economics trial to reduce the overprescribing of antibiotics, June 2018. Available at: http://www.health.gov.au/internet/main/publishing.nsf/content/Nudge-vs-Superbugsbehavioural-economics-trial-to-reduce-overprescribing-antibiotics-June-2018]

Delayed prescribing for specific conditions, like acute respiratory tract infections, can be implemented in several different ways. Systematic review of randomized controlled trials using delayed prescribing suggest that the lowered antibiotic use did not make a difference in the clinical outcomes. [Sargent, L., McCullough, A., Del Mar, C., & Lowe, J. (2016). Is Australia ready to implement delayed prescribing in primary care? A review of the evidence. Aust Fam Physician, 45(9), 688-690. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27606375]

Alternatives to antibiotic prescribing—an herbal remedy for palliating the symptoms of a viral infection not requiring an antibiotic—have been developed as part of Thailand’s Antibiotic Smart Use project. [Sumpradit N, Chongtrakul P, Anuwong K, Pumtong S, Kongsomboon K, Butdeemee P, Khonglormyati J, Chomyong S, Tongyoung P, Losiriwat S, Seesuk P. Antibiotics Smart Use: a workable model for promoting the rational use of medicines in Thailand. Bulletin of the World Health Organization 2012; 90: 905-913. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3524958/]

Opportunities for Innovation

—How can targeting specific conditions—which seldom require antibiotics—be assessed effectively and incentives given to providers not to overprescribe antibiotics in such cases?

—Are there any diagnostic approaches—when combined with present symptoms and signs in the patient—that could improve rational use and decrease inappropriate use of antibiotics?

—What new approach—perhaps building on previous efforts from behavioral economics to audit-and-feedback—might motivate prescribers in outpatient settings to reduce overprescribing of antibiotics?

—What other practices—such as substituting antibiotics with an herbal alternative for palliating viral symptoms—might change the sociology of practice and address patient expectations of treatment, but not result in overuse of antibiotics?

—How can delayed prescribing be implemented in resource-limited settings? Might mobile phones help implement such an approach?

Pharmacies

At the outpatient pharmacy, patients may seek antibiotics for treating bacterial infections. Pharmacists play an important role in ensuring that patients receive the prescribed medicines, do not have a history of drug allergies to the medication, and are properly educated about the appropriate way to take the antibiotic course. In too many countries, however, antibiotics can be obtained over the counter without prescription. Pharmacists dispense antibiotics, but sometimes, the full antibiotic course dispensed for treatment might not be affordable to the patient. Problems of stockouts or substandard or falsified antibiotics can also create problems. Some pharmacy outlets might be in the informal sector and not be compliant with licensing or other regulations. Financial incentives may favor dispensing of brand-name antibiotics when lower-cost generics might be available. Packaging of antibiotics might be broken when partial courses of antibiotics are dispensed, and patient instructions and warning labels on the packaging might be missed.

Challenges include:

• Dispensing without a healthcare provider’s prescription
• Stockouts
• Substandard or falsified antibiotics
• Financial incentives influencing dispensing of brand-name vs. generic antibiotics
• Pharmacies operating outside the formal sector
• Need for effective packaging, warning labels and patient instructions

Background Literature

Multiple studies document the knowledge, attitudes and practices of community pharmacists towards antimicrobial stewardship (e.g., in Malaysia and Pakistan).

Pharmacists can play an important role in enabling more appropriate use of antimicrobials and providing education to both patients and providers in support of this goal. [Sakeena MHF, Bennett AA, McLachlan AJ. Enhancing pharmacists’ role in developing countries to overcome the challenge of antimicrobial resistance: a narrative review. Antimicrob Resist Infect Control, 2018; 7:63. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29744044]

With the introduction of electronic systems to capture data and mobile technologies to share such data, new opportunities for engaging pharmacists more deeply in antimicrobial stewardship have surfaced [Gilchrist M, Wade P, Ashiru-Oredope D, Howard P, Sneddon J, Whitney L, Wickens H. Antimicrobial Stewardship from Policy to Practice: Experiences from UK Antimicrobial Pharmacists. Infect Dis Ther 2015; 4(Suppl1):51-64. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569645/pdf/40121_2015_Article_80.pdf]

Current Efforts

Providing an alternative to small retail drug shops, a program in Tanzania has supported accredited drug dispensing outlets (ADDOs) with “extensive training, business incentives, authorization to dispense a limited list of antimicrobials and other medicines to treat common conditions, regulatory enforcement of practice standards, and efforts to affect customer demand.” The role of ADDOs in ensuring improved access to antimicrobials has been studied. [Chalker JC, Vialle-Valentin C, Liana J, Mbwasi R, Semali IA, Kihiyo B, et al. What roles do accredited drug dispensing outlets in Tanzania play in facilitating access to antimicrobials? Results of a multi-method analysis. Antimicrob Resist Infect Control 2015; 4:33. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4545914/pdf/13756_2015_Article_75.pdf]

Several companies (e.g., PharmaSecure, Sproxil, and mPedigree) are providing authentication of drug packages, from pharmaceutical manufacturing plant to pharmacy outlet, and these can help address the challenge of substandard and falsified antibiotics.

Opportunities for Innovation

—Could pharmacy-based approaches to support better dispensing practices of antimicrobials build upon the experience of accredited drug dispensing outlets?

—Could community pharmacist efforts to engage in health education and disease prevention be extended to improving antibiotic use?

—Could other data, from prescribing to medication adherence to antimicrobials, be derived from authentication systems of drug packages?

PATIENTS

Patients present to the healthcare delivery system, oftentimes when self-care will not likely resolve signs or symptoms of illness and sometimes when traditional medicine has failed. Patients present to hospitals and clinics for evaluation and treatment as well as to pharmacies for obtaining medicines like antibiotics. Access challenges can be characterized by 5A’s—accessibility, availability, acceptability, affordability and accommodation. For example, the diagnostic can sometimes be more expensive than just treating presumptively or empirically with antibiotics (that is, without making the diagnosis before treatment).

Patients may have expectations of antibiotic treatment even when the illness is viral and not treatable by such drugs. As end-users of antibiotics, patients also influence rational use of these drugs. Providers may feel compelled to prescribe these drugs, but perhaps less so when alternatives to antibiotic prescribing exist. These approaches range from watchful waiting strategies (delaying the dispensing of an antibiotic till it becomes clear an antibiotic is truly necessary) to having an herbal medicine substitute capable of palliating the symptoms of a viral infection (as Thailand’s Antibiotic Smart Use project has done). When empiric treatment with antibiotics are more expensive than the diagnostic to decide on the use of such treatment, this can also present a quandary for patients and providers. Patients may incur out-of-pocket costs that also preclude their filling of prescribed antibiotics.

The paradox of overuse and underuse of antibiotics is captured in the contrast between treatment of pneumonia and diarrhea. According to UNICEF, more than one out of every four children that die under age 5 will be claimed by pneumonia or diarrhea. Yet of those with pneumonia, fewer than one in three will be treated with antibiotics. Of those with diarrhea, fewer than four in ten will received oral rehydration therapy or continued feeding. Rather many of these children will be treated inappropriately with antibiotics.

Background Literature

A multi-country survey carried out by the WHO revealed that well over half of respondents across the 12 countries erroneously thought that antibiotics could treat viral infections such as colds and influenza. Nearly a third would also stop antibiotics when they felt better, not when the treatment course was completed as prescribed.

Current Efforts

The Swedish strategic program against antibiotic resistance (STRAMA) built a nationwide collaboration that involved professional groups, government, and a One Health perspective. Over a twenty-year period, significant decreases in the use of prescribed antibiotics occurred, and Swedish citizens have among the highest overall knowledge of antibiotics and drug resistance in a European survey. Half of Swedes surveyed can recall being told not to take antibiotics unnecessarily over the past year.

Thailand Antibiotic Smart Use project has fielded several key messages targeting patients: 1) debunking that antibiotics are anti-inflammatory agents; 2) antibiotics are classified under the country’s Drug Act as drugs with potentially serious adverse effects; and 3) three commonly treated conditions—acute diarrhea, uncomplicated wounds and upper respiratory infections—do not require antibiotics. The project also enabled consumers to use a pharyngeal mirror and in pharmacies to prompt them to consider whether a sore throat required antibiotic treatment or not.

Opportunities for Innovation

—How can consumers be empowered to address the 5A’s of access to antibiotics and help ensure rational use?

—How can the expectations of patients to receive an antibiotic be reshaped? How can individual efforts to ensure rational use of antibiotics in the healthcare delivery system become collective action?

—Are there approaches like citizen science (e.g., test kits for substandard or falsified drugs or identifying drug-resistant pathogens in food) that can help mobilize public awareness to tackle AMR in the healthcare delivery system? [Note: This year’s Innovate4AMR competition focuses on the healthcare delivery system, not on food production.]

–What strategies can address consumer concerns over delayed prescribing (watchful waiting) to conserve the use of antibiotics?

 

OTHER STAKEHOLDERS

PAYERS

Payers such as governments, church-based healthcare systems, or private insurers can each signal providers as to how to use antibiotics. These signals can take the form of financial or non-financial incentives. Pay-for-performance approaches can influence provider behavior, just as some incentives also pay providers to prescribe more antibiotics. Significant work still needs to be undertaken to realign such incentives to encourage rational use of antibiotics.

GOVERNMENT

Governments can adopt National Action Plans on antimicrobial resistance, as called for under the Global Action Plan on Antimicrobial Resistance. A key component of these plans focuses on the healthcare delivery system, but not in isolation from other sectoral contributions. Governments can support, with both technical and financial resources, the implementation of efforts to tackle AMR; establish a regulatory framework and put expert guidelines in place; and mandate collection of data to ensure effective monitoring for accountability.

ACADEMIA

Universities and professional schools training future physicians, nurses, pharmacists and other healthcare professionals can include AMR as part of their curricula and can make this as part of what defines professional competency. Such institutions also can conduct research and pilot new interventions that might address AMR in its local context.

CIVIL SOCIETY

Non-governmental organizations, from professional societies to consumer groups, play a critical role in supporting effective regulation, credentialing, and certification of key actors, from healthcare providers to industry, to engage in more rational and responsible use of antibiotics. These groups can also mobilize public and policymaker awareness of AMR.

DRUG MANUFACTURERS / INDUSTRY

Industry can encourage rational use of antibiotics by complying with appropriate package dosing and labeling, making full treatment courses affordable, and not mispromoting the use of antibiotics where not indicated. Authentication technologies (such as scratch-off codes that verify the integrity of the package when texted back) can help with pharmacovigilance efforts.

WHOLESALERS

Wholesalers are responsible for ensuring the integrity, quality, and reliability of the supply chain of antibiotics. Along with drug manufacturers, they contribute importantly to the affordability and the availability of antibiotics. Effective inventory management can prevent stockouts, and efficient procurement practices, affordable pricing.

 

RELATED SYSTEMS

FOOD PRODUCTION SYSTEM

The use of antibiotics in food production can result in drug-resistant bacteria entering the diet of the population. Food-borne infections, such as typhoid fever from contaminated food products, could become resistant to first-line treatment of antibiotics.

WASH (Water, Sanitation and Hygiene)

Potable water, good sanitation and hygiene practices can all reduce the overall burden of infectious diseases in a population. By doing so, antibiotic treatments can be averted, and rising drug resistance, in part, stemmed.

Other References/Resource Links

Rogers Van Katwyk, S., Jones, S. L., & Hoffman, S. J. (2018). Mapping educational opportunities for healthcare workers on antimicrobial resistance and stewardship around the world. Hum Resour Health, 16(1), 9. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5799960/pdf/12960_2018_Article_270.pdf

[This reference has a table with antimicrobial stewardship educational opportunities]

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