The Global Threat of Antimicrobial Resistance and the Challenges and Needs of Developing Countries

The antimicrobial resistance crisis will affect developing countries the most. Yet they are not well prepared to tackle it. This is part of a paper used by Martin Khor when speaking at a panel at the High-Level Event on AMR at the UN General Assembly in September 2016 and updated for the Asian Workshop on AMR in March 2018.

By Martin Khor, South Centre

Antimicrobial resistance has become a major global health crisis

Antimicrobial resistance (AMR) is a major and serious problem.  It represents possibly the greatest global crisis in public health in the world today, akin to climate change as the top environmental problem.

Antimicrobial resistance is resistance of a microorganism to an antimicrobial drug that was originally effective for treatment of infections caused by it.  Resistant microorganisms (including bacteria, fungi, viruses and parasites) are able to withstand attack by antimicrobial drugs, such as antibacterial drugs (e.g. antibiotics), antifungals, antivirals, and antimalarials, so that standard treatments become ineffective and infections persist, increasing the risk of spread to others.

Resistance by bacteria and other microbes to antibiotics and other medicines may be a natural process, as the microbes causing diseases evolve through time in response to the medicines.  However, the rate of resistance is accelerated and the scope of resistance is broadened by several factors:   the inappropriate use of antibiotics, due to inappropriate prescribing and dispensing; inappropriate marketing methods and sales promotion;  lack of awareness by patients;  the inappropriate and widespread use of antibiotics in the animal husbandry and agriculture sector, which passes on resistant microbes to humans;  the spread of resistance through the environment; and the existence of certain genes that specialize in accelerating and spreading resistance among bacteria, thus greatly increasing the rate and spread of resistance to many species of bacteria that cause diseases.

AMR is now a global crisis, with many pathogens becoming resistant to many antibiotics.  As leading public health officials and senior scientists have warned, we are now entering a post-antibiotics world, in which it is increasingly difficult to treat simple ailments and dangerous diseases.  The incidence of multi-drug resistance has risen significantly, and for a few diseases there is almost no cure left.   In 2012, World Health Organization Director-General Dr. Margaret Chan warned that every anitibiotic ever developed was at risk of becoming useless.  “A post-antibiotic era means in effect an end to modern medicine as we know it.  Things as common as strep throat or a child’s scratched knee could once again kill.”     The Chief Medical Officer of the United Kingdom, Dame Sally Davies, warned in 2013 of a “catastrophe” of AMR being so widespread that we would be back to a 19^th century situation of a pre-antibiotic era when many diseases could not be treated.

The UN General Assembly High-Level Event and Political Declaration on AMR

A landmark development at global level is the adoption on 21 September 2016 of a Political Declaration on AMR by the heads of states and governments at a high level event on AMR.  It was subsequently formally adopted by the General Assembly.

Many political leaders and Ministers spoke at the event on the need to fight the AMR crisis.  The Political Declaration recognized that antibiotic resistance is the “greatest and most urgent global risk” and that “due to AMR many 20th century achievements are being gravely challenged, particularly the reduction in illness and death from infectious diseases…”   This is the first ever statement by the heads of all the countries that recognize the AMR crisis and in which they pledge to take action.

The Declaration stressed the need of developing countries to obtain financial resources.  It also stressed that “affordability and access to existing and new antimicrobial medicines, vaccines and diagnostics should be a global priority.”

On the need for innovation, the Declaration recognised the importance of delinking the cost of investment in R&D from the price and volume of sales so as to facilitate equitable and affordable access to new medicines, diagnostic tools and vaccines.

The declaration established a task force of agencies (co-chaired by the WHO and Secretary-General’s office) which would provide guidance for global action on AMR and requested the UN Secretary-General (UNSG) to report on progress of implementation of the Declaration and to make further recommendations.

In 2017, the Interagency Coordination Group was established by the UNSG to follow up on the Declaration.  It is made up of individual experts (many drawn from health ministries) and representatives of UN and other international organisations.  The IACG has a plan of action, and has held three meetings to date.  It also established six sub-groups to come up with analysis and recommendations. The report of the IACG will be submitted to the UNSG who will present his own report to the UN General Assembly in 2019.   The IACG will be holding more consultations with the member states and with public interest groups.  It is important for developing countries’ policy makers and NGOs to engage with the IACG.

The global fight against AMR has to involve the developing countries as a top priority

It is to be expected that the developed countries will take the lead in the global fight against AMR.  This is due to the greater availability of financial resources, and higher levels of scientific knowledge, research capability and technology as well as institutional and organizational capabilities including in the health care sector.

However, the developing countries will have to play a central role in the global battle against AMR, since it is in the developing countries that the majority of the world population reside, that there is the highest number (and in some cases highest incidence) of people suffering from drug-resistant diseases, and that pathogens with the genes specializing in spreading resistance have been mainly found in patients in developing countries.  Moreover, in an increasingly globalised world with a high degree of travel and trade, there can be the easy spread of drug resistant bacteria and diseases.

Therefore, the special needs and interests of the developing countries have to be given the highest priority in the global fight against AMR if we are to make adequate progress.

Developing countries are becoming more aware of the AMR crisis

Political leaders and public health officials in developing countries are becoming more aware of the AMR crisis.

At the Summit meeting of the Group of 77 and China, which has around 130 members from developing countries, held in Santa Cruz (Bolivia) in May 2014, the political leaders of the Group adopted a Declaration which included the following paragraph 66:

“We are concerned about the increasing problem of antimicrobial resistance to existing drugs, including those against TB and malaria.  As a result, increasing numbers of patients, especially in developing countries, face the prospect of dying from preventable and/or treatable diseases. We urge the international health authorities and organizations, especially WHO, to take urgent action and to work together upon request with developing countries that do not have adequate resources to address this problem.”

However, in most developing countries, the public is still lacking knowledge and awareness of the threat of AMR, while coordinated and systematic action is also at only a beginning stage.  Therefore, much more has to be done.

People in developing countries are most affected by AMR

People in developing countries will be most affected by the AMR crisis.   At present AMR is estimated by the UK-sponsored Review on AMR to globally cause 700,000 deaths annually (and this is a low estimate).   The annual deaths attributable to AMR is projected to rise to 10 million in 2050.  Of these deaths, it is projected that 390,000 will be in Europe, 317,000 in North America, 22,000 in Oceania, 4.7 million in Asia, 4.2 million in Africa and 392,000 in Latin America.

For most diseases the majority of people affected by AMR are in developing countries.   The Review on Antimicrobial Resistance (2014: p. 9) concludes that “countries that already have high malaria, HIV or TB rates are likely to particularly suffer as resistance to current treatments increases.”  Particular countries at risk include India, Nigeria and Indonesia (malaria) and Russia (TB) and Africa will suffer greatly as the HIV and TB co-morbidity is likely to get worse.

The Review also estimates that 300 million people are expected to die prematurely because of drug resistance over the next 35 years (i.e. 2015 to 2050) and world GDP will be 2 to 3.5% lower than it otherwise would be in 2050.  Between now and 2050 the world can expect to lose US$60 to 100 trillion of economic output if AMR is not tackled.   OECD countries are expected to have US$20-35 trillion in cumulative loss of output by 2050; which means that about US$40-65 trillion or two-thirds of the losses will be borne by non-OECD countries.

The case of tuberculosis is illustrative.  The Review on Antimicrobial Resistance (2016) found that of  “the 10 million deaths that might be associated with drug resistance each year by 2050, around a quarter will come from drug-resistant strains of TB.”   Most of these anticipated cases and deaths from resistant TB will be from developing countries, although TB is also affecting several developed countries.

The majority of people affected by increasing resistance to drugs treating malaria and to the first-line treatments for HIV-AIDS are also from developing countries.   Pathogens that are increasingly resistant to powerful antibiotics (E coli, K. pneumonia, S. Aureus, salmonella, shigella, gonorrhoea) are prevalent in developing countries.

Policy makers and the public in developing countries should therefore recognize that the AMR crisis is mainly taking place in their countries and that they have to give the highest priority to addressing it. On the other hand, the international community has to pay special attention to the needs of developing countries and to assist them in addressing the AMR crisis.

In recent years, there has been the discovery of at least two types of genes (NDM-1 and MCR-1) that have the characteristic of being able to make bacteria highly resistant to known drugs and to also spread from one species of bacteria to other species through horizontal gene transfer.  Bacteria containing these genes were first found in developing countries, and their presence is now confirmed in many other countries.  The discoveries of NDM-1 and MCR-1 add urgency to the task of addressing anti-microbial resistance.

Developing countries face many challenges in addressing AMR

Developing countries face many challenges in addressing AMR.  There is a lack of awareness, expertise, funds, technical equipment, personnel and political will to take the range of actions required.  These are serious obstacles to the implementation of AMR action plans.

Another issue is that AMR is a problem that involves the mandate of several sectors and thus government Ministries or departments.  The sources of the problem are in health, agriculture and livestock, and the environment.  To educate the public, the education and information departments need to be involved.  The involvement and commitment of all these departments are required in the multi-faceted fight against AMR.  Obtaining the commitment and coordination of the various sectors requires great effort and the commitment of political leaders at the highest level.  It is not easy to achieve this.

The developing countries also have other problems that compete with AMR for attention and resources.  Although it is a very major problem, AMR is a silent killer rather than an obviously critical issue compared to other issues within and outside the health sector (such as malnutrition, infection outbreaks and epidemics; conflict and terrorism; floods, drought, water scarcity and climate change; unemployment, poverty, migration and refugees).

In the competition for scarce funds and personnel, it is difficult for AMR to obtain the resources and attention it deserves.

Developing countries also need affordable access to existing and new antibiotics and other microbials 

Another major issue of concern to developing countries is their need for affordable access to antimicrobials, including existing and future ones.  Even when the medicines are not patented and there is competition from generics, many poor patients cannot afford treatment.  If the antimicrobials are patented, the prices escalate and pose a big barrier to access.  As resistance builds, 2^nd and 3^rd line drugs are needed to treat existing diseases; these new drugs are likely to be patented and expensive.

There are several examples of the high cost of new anti-microbials that is a barrier to access.

• Two new drugs for treating drug-resistant TB which have been recommended by WHO have been on the market for four years, but only 4,800 people with DR-TB in 2016 were treated with them, according to Médecins Sans Frontières (MSF). Only 469 people received delamanid and just over 4,300 received bedaquiline.  Thus, fewer than 5% of people needing the drugs received them while others continued to be treated with older and more toxic regimens that cure only 50% of people treated and cause severe side effects.  More than half a million people were infected with DR-TB in 2015.   In an earlier statement in 2016, MSF said the price of a single course of delamanid in developing countries was $1,700 per person, and it called for a 98% price reduction. Delamanid has to be taken with several other drugs to effectively treat DR-TB, and the regimens, without delamanid, already cost $1000-4500 per treatment course at lowest prices available in developing countries, which is unaffordable for governments.  MSF is advocating a target price of $500 per treatment course for DR-TB.
• The prices of second and third line HIV medicines are much higher than first-line medicines. Patients who no longer respond to first-line treatment (due to resistance) have to switch to the newer medicines but face cost and access problems.  According to MSF, in 2015 the lowest available price of a first-line one-pill-a-day combination (tenofovir+emtricitabine+efavirenz) was $100 per person per year.  But the lowest price of newer drugs (or ‘salvage’ treatments) needed by people who have run out of other treatment options was $1,859 per person per year (raltegravir+darunavir+etravitine).  This is 18 times the price of first-line therapy and over six times the price of second-line combination.  The MSF report finds that “prices of older HIV drugs continue to decline while newer drugs remain largely priced out of reach. This is in large part because pharmaceutical corporations maintain monopolies that block price-lowering generic competition.”
• The new drug for Hepatitis C, sofosbuvir, was introduced in the US market at US$80,000 for a course of treatment. In middle-income developing countries that were not offered a voluntary license by the drug company (Gilead), the price varied from about $10,000 to $40,000.   Sofosbuvir, usually taken in combination with another drug, has an efficacy rate of 95% and less side effects, compared to a much lower rate with more side effects of older regimens.  But the price of sofosbuvir is out of reach to most people and governments in  developing countries (and developed countries too).  The high prices could be maintained due to a patent owned by Gilead.  Malaysia in 2017 issued a compulsory license for sofosbuvir.  A local firm is now importing generic sofosbuvir from Egypt.  The lowest price offered by Gilead to the government for sofosbuvir was RM50,000, according to the Health Minister.  The government has now negotiated to obtain a generic version of sofosbuvir at RM 1,000 (US$250) a patient.  The government is now offering the combination of sofosbuvir and daclastavir at government hospitals free;  it will bear the cost of treating patients.  Previously, some patients had to pay RM300,000 for a treatment course. Malaysia has 400,000 people with Hepatitis C.  According to the news report, 23,000 patients in the Health Ministry’s list will be treated in stages, with 2,000 treated in 2018.

These three examples illustrate that access to new antimicrobials being developed will be a major issue.  With regard to antibiotics, the new antibiotics should be considered international public goods accessible to people especially in developing countries which do not otherwise have financial resources to afford them if they are sold at monopoly prices.

Developing countries also need affordable access to vaccines as well as laboratory and diagnostic equipment.

Affordable and reliable access is required not only for new antimicrobials but also for existing ones.  Many people in developing countries still do not have access to the existing medicines, either because they are not available in the market or the public hospitals, or they are unable to afford to buy them.  According to presenting key stakeholder groups including ReAct, GARDP and the European Society of Clinical Microbiology and Infectious Diseases, in a Commentary in the Lancet Infectious Diseases journal, unsustainable production and supply of old antibiotics is becoming a serious global problem that further limits the treatment options for common bacterial infections and this is adding to the worldwide crisis of antimicrobial resistance.   “Shortages and sudden price increases of antibiotics have been reported, indicating a fragile supply system.  Consequences might include worse clinical outcome, accelerated resistance development and increased costs for the individual and society at large,”  according to one of the authors, Thomas Tangden, Medical Director at   ReAct.

When patents become a barrier to access, countries have the policy option of making use of the flexibilities in the WTO’s TRIPS Agreement, such as establishing patent criteria that improve the quality of patents by awarding patents only for genuine inventions; and issuing compulsory licenses or government use orders to increase market competition by enabling the production and importation of generics.  However, countries that exercise their right to make use of these flexibilities often find strong opposition from originator companies and their governments.  The legitimate use of flexibilities should not be opposed.

It is important that the principle of access is given priority when evaluating and developing the models for research and development of new antimicrobials.

The Political Declaration on AMR places great emphasis on access. In many parts, the Declaration mentions affordable access to existing and new antimicrobials as an important principle and objective.

The issue of financing and of access was prominent in the Political Declaration of the UNGA

The Political Declaration of the UNGA on AMR is very strong on capacity building, access to medicines, technology transfer and financial support to developing countries.  It says (in  Para. 10.d) that the heads of state and government  “underline further that affordability and access to existing and new antimicrobial medicines, vaccines and diagnostics should be a global priority.”  Para. 10.f says the heads of state and government want to “enhance capacity building, technology transfer on mutually agreed terms and technical assistance and cooperation for controlling and preventing antimicrobial resistance, as well as international cooperation and funding to support the development and implementation of national action plans, including surveillance and monitoring, the strengthening of health systems and research and regulatory capacity, without jeopardizing, in particular in the case of low- and middle-income countries, health or posing barriers for access to care.”

At the WHA in May 2017, several developing countries, including Brazil and India, stressed the need to place access to affordable existing and new antibiotics and diagnostic tools as priority issues, as it was not enough to take action on the control and distribution of antibiotics.  They also highlighted the need to use innovation models based on the “delinkage” principle, to ensure affordable medicines.  These two issues of access and delinkage were prominent in the UNGA Political Declaration, but were not given due recognition in the Development and Stewardship Framework document, complained Brazil.

The need for an innovation model consistent with access to new antibiotics

It is imperative to develop new antimicrobial medicines, diagnostic tools, vaccines and other products, as a major part of addressing the AMR crisis.  There are deep-rooted problems with R and D in relation to antibiotics.  One is that there have been few or no new categories of antibiotics discovered in the past two to three decades, and there are few promising new products in the present pipeline.   A reason for this may be that there is less profit to be made from antibiotics compared to drugs for diseases which require long-term treatment.

Second is that the dominant R&D model links medicine prices to the cost of R&D, with patents for the company, which results in high prices for new drugs which are unaffordable to most people in developing countries.  There is thus a need for a R&D model that is compatible with access to medicines, one which delinks the cost of innovation from the price of new medicines as well as from sales volume.  This is often referred to as innovation models based on the de-linkage principle.

There are at least two main strands of thinking on what kind of R and D model to encourage.  The first is to continue with the dominant model but increase the incentives to companies by providing more R and D grants to them and allowing an extended patent term for new antibiotics in the hope that this will provide more incentives to the major drug companies and result in new products.  The downside is that this increases the period of monopoly and high prices, and worsens the problem of access.

The second is to establish public funding by governments and donations by charities, so that the cost of innovation is not borne by the companies.  The proprietary rights to the new products would belong to the public fund or charity, which has the option of providing licenses freely to companies or institutions, at least to those from developing countries; or licenses granted to companies would be linked to conditions that favour access. This would delink the cost of innovation from the prices of the new products, which can be set at affordable levels.  The WHO has been exploring options for new partnerships for open collaborative models of R and D.  It is partnering with the Drugs for Neglected Diseases initiative to set up a non-profit partnership, the Global Antibiotic Research and Development Facility to develop new affordable antibiotics that will also be subjected to a conservation scheme.

The Political Declaration on AMR adopted by political leaders at the UN is clearly in favour of R and D activities that are closely linked to access to medicines and that are in line with the “delinkage” model.  It has a lengthy paragraph (10.c) dealing with R and D.   It states that  heads of states and governments “underline also that all research and development efforts should be needs-driven, evidence-based and guided by the principles of affordability, effectiveness and efficiency and equity, and should be considered a shared responsibility:  in this regard we acknowledge the importance of delinking the cost of investment in research and development on antimicrobial resistance from the price and volume of sales so as to facilitate equitable and affordable access to new medicines, diagnostic tools, vaccines and other results to be gained from research and development.”

The UN Secretary General’s High-Level Panel on Access to Medicines states that its report “emphasizes that market-based models of innovation for AMR are unsustainable. Funding for R&D to address AMR and related challenges must be operationalized through delinkage models. Indeed, the challenge of AMR represents an important and incontestable context in which the viability of delinkage innovation models can be fully explored.”

Summary of key points on meeting the needs of developing countries

Programmes dealing with implementing actions on AMR should include the following points:

• Fully take into account the challenges and needs of developing countries.
• Strong international cooperation for building capacity of developing countries to address AMR.
• Mobilising of financial resources to support capacity building and implementation of AMR action plans in developing countries.
• Establish a global fund for capacity building in developing countries on AMR issues, to be based in the UN, and linked to implementing the Global Action Plan on AMR. Meanwhile, governments should be encouraged to establish their own funds or allocate part of their ODA to assist developing countries to address AMR.
• Technology transfer and the provision of technical equipment including diagnostics and know how to developing countries on grant or concessional terms.
• Ensuring affordable access to existing and new antimicrobials, vaccines and diagnostics, especially to people in developing countries.
• Developing and encouraging R&D models which delink the price of anti-microbials and other products from the cost of R&D; including where the innovation costs are financed through public funds and charities, and the license to produce the new products is available cheaply or at low cost, at least to companies and institutions in developing countries.
• Support to developing countries for capacity building and financing of the comprehensive range of activities in addressing AMR at national level, including prevention of infections, appropriate use of antibiotics, new regulations including on marketing, prescription and dispensing of drugs and their enforcement, reform of antibiotic use in agriculture, improvement of practices in hospitals and clinics, educating the public, etc.

Recent information on the extent of resistance

A good description of the extent of the AMR has been given by WHO in its Fact Sheets on AMR.   The following is a summary of the WHO findings as at January 2018:

• Antimicrobial resistance threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi.
• Patients with infections caused by drug-resistant bacteria are at increased risk of worse clinical outcomes and death than patients infected with non-resistant strains of the same bacteria. They also consume more health-care resources than patients having non-resistant strains of the same bacteria.
• There are high proportions of antibiotic resistance in bacteria that cause common infections (e.g. urinary tract infections, pneumonia, bloodstream infections) in all regions of the world.
• Resistance to Klebsiella pneumoniae (common intestinal bacteria that can cause life threatening infections) to a last resort treatment (carbapenem antibiotics) has spread to all regions. In some countries, because of resistance, carbapenem antibiotics do not work in more than half the people treated for K. pneumoniae infections.  K. pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, and infections in newborns and intensive-care unit patients.
• Resistance in E. coli to a widely used medicine for treating urinary tract infections (fluroquinolone antibiotics) is very widespread. This treatment is now ineffective in over half of patients in countries in many parts of the world.
• A high percentage of hospital-acquired infections are caused by highly resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant Gram-negative bacteria. People with MRSA are 64% more likely to die than those with a non-resistant form of S. aureus, which is a common cause of severe infections in the community and hospitals.
• In 2016, there were 490 000 new cases of multidrug-resistant tuberculosis (MDR-TB). Only a quarter of these were detected and reported. Extensively drug-resistant tuberculosis (XDR-TB) has been identified in 121 countries. MDR-TB requires treatment courses that are much longer and less effective than those for non-resistant TB. Among new TB cases in 2016, 4.1% were MDR-TB (19% for those previously treated for TB). About 6.2% of people with MDR-TB have XDR-TB.
• As of July 2016, resistance to first-line treatment for P. falciparum malaria (artemisinin-based combination therapies or ACTs) has been confirmed in 5 countries (Cambodia, Laos, Myanmar, Thailand, Viet Nam) of the Greater Mekong subregion. Patients with artemisinin-resistant infections recover if they are treated with an ACT containing an effective partner drug.  However, along the Cambodia-Thailand border, P. Falciparum has become resistant to almost all available antimalarial medicines.  The spread or emergence of multidrug resistance, including resistance to ACTs, in other regions could jeopardize important recent gains in malaria control.
• Treatment failures due to resistance to treatments of last resort for gonorrhoea (third-generation cephalosporin antibiotics) have been confirmed in at least 10 countries. The new updated WHO guidelines for gonorrhoea do not recommend quinolones (a class of antibiotic) due to widespread high levels of resistance. Gonorrhoea may soon become untreatable as no vaccines or new drugs are in development.
• In 2012, WHO reported a gradual increase in resistance to HIV drugs, albeit not reaching critical levels. Since then, further increases in resistance to first-line treatment drugs were reported. In 2010, 7% of people starting antiretroviral therapy (ART) in developing countries and 10-20% in developed countries had drug-resistant HIV.  In some countries, resistance of 15% or more is reported for those starting HIV treatment, and up to 40% among those re-starting treatment. Those who have HIV resistant to first-line treatment require second and third line regimens but these are 3 and 18 times more expensive respectively than first-line drugs.

Actions needed to address AMR at national level

Boosting the capacity of developing countries to take required actions is of key importance.  The actions that need to be taken at national level include:

• Research in science, including analysis of bacteria mutation, gene transfer, rates and ways of the spread of resistance, and AMR in the food chain.
• Vastly improving surveillance and data collection on resistance in various pathogens to various drugs, and resistance of bacteria in food-related animals, in food, and in the environment.
• Improve and upgrade laboratory equipment especially diagnostic tools, to enable better diagnosis, to distinguish between bacteria and viruses, and between resistant and non-resistant bacteria (and pathogens) so as to enable appropriate treatment.
• Infection control in hospitals, including hygiene, upgrading of rooms and theatres, equipment, air-flow systems etc.
• Infection control through provision of safe water, proper sanitation and habitat and a clean environment.
• Formulating and implementing a national policy for rational and appropriate use of antibiotics and other anti-microbials.
• Regulation and enforcement in the sale, prescription and dispensing of anti-microbials.
• Guidelines or regulations for medical personnel, hospitals and clinics on the appropriate use of antibiotics, and on relations with industry sales representatives.
• Regulating drug companies in marketing practice to improve their role in appropriate drug use, and address effects of incentives to sales personnel and to medical and veterinary personnel that are linked to volume of antibiotic sales.
• Regulation of the agriculture and livestock sector to phase out the non-therapeutic use of antibiotics, as this inappropriate use is a major factor in the AMR crisis. As a first step, antibiotics that are used for treatment of life threatening diseases in humans should be prohibited as use in animals as growth promoters.
• Addressing the contamination of the environment by residues of antibiotics, including those emitted by drug factories and medical facilities.
• Educating the consumer and community on the appropriate use of antibiotics.
• Formulate policies enabling affordable access for the public to existing and new antibiotics and other antimicrobials.
• Establishing a national action plan on AMR and the institutional framework for implementation, including coordination within the health sector and with other Ministries including of Agriculture, Education, Information.
• Boosting the capacity of health related NGOs, the media and educational institutions to take on AMR issues as a priority.
• Mobilise domestic and external funds to enable implementation of the national AMR plan and activities.

Making resources available for developing countries

In order to implement the necessary actions, the developing countries require international cooperation for the following:

• Obtaining adequate financial resources for addressing AMR. Developing countries will have to mobilise domestic resources to carry out activities to address AMR.  However some of them, especially lower income countries, will require international funding to augment the domestic resources, due to the high cost involved and the competing issues that also require financing.  Countries should prepare their comprehensive AMR action plans together with cost estimates and a budget with estimates of the resources that can be mobilized nationally and resources that are sought from international cooperation.
• Obtaining Equipment and Technology needed to address AMR. This would include equipment for diagnosis, for making hospitals and clinics AMR-proof, scientific research, and innovation.
• Upgrading hospital facilities to improve infection control, surveillance and diagnosis, the ward and surgery environment, to minimise the spread of infections (especially resistant infections) within the hospitals and to provide an appropriate environment for patients with resistant infections.
• Obtaining antibiotics and other anti-microbials to treat patients including those with ailments caused by drug-resistant pathogens.
• Costs of phasing out the non-therapeutic use of antibiotics in the animal husbandry sector.
• Costs of addressing the environmental aspects of AMR.
• The recruitment and training of adequate numbers of personnel including for management and coordination of the AMR action plan, surveillance, administration and enforcement of guidelines and regulations.
• Boosting the capacity of communities, civil society organisations, educational institutions and the media to raise public awareness and take other actions relating to AMR.

An international fund, or a number of funds, should be established to assist developing countries to meet the above costs of addressing AMR.

Part of the fund should be used for making available technical equipment that may be required for surveillance, diagnosis and treatment.