The Antimicrobial Resistance Crisis: How Neoliberalism Helps Microbes Dodge Our Drugs

Antimicrobial Resistance: The Problem

Microorganisms are naturally adaptive to their surroundings, with AMR being an inherently natural process; however, the industrialization and excessive use of antimicrobials since the 1940s have greatly accelerated this process.^2,5 Antimicrobials are used inappropriately around the world, often being prescribed without need, accessible over the counter or without a prescription in many countries, or used by patients who do not comply with the indicated treatment length or dosage.^1,2,5 As a result of decades of overuse and misuse, drug-resistant infections are becoming more common, ⁸ with antibiotic-resistant hospital-acquired infections estimated to cause 99,000 deaths per year in the United States alone. ² In fact, multi-drug-resistant hospital-acquired infections are a leading cause of death worldwide among hospitalized patients. ⁹

Despite these alarming statistics and the fact that AMR has been labeled a “global concern” since the 1990s – and, in more recent years, a “global crisis” – progress in combating this threat on a global scale has been surprisingly limited. While new national policies and health promotion strategies have decreased antimicrobial use in certain areas, data from 76 countries show that antibiotic consumption (expressed in defined daily doses [DDDs]) increased by 65% from 2000 to 2015.¹⁰

Timeline of Action Against Antimicrobial Resistance

AMR was first presented as a shared global problem in the 1980s, leading to the formation of the Alliance for the Prudent Use of Antibiotics, an international group focused on promotion of appropriate antimicrobial use and investment in AMR surveillance systems. ¹⁷ However, this had little immediate impact upon prescribing, and it was not until Great Britain’s bovine spongy encephalitis scare in the 1990s that major governmental agency funding established an AMR surveillance system, named the European Antimicrobial Resistance Surveillance System (EARSS, later known as EARS-Net). ¹⁷ In 2001, the WHO recognized AMR as a concern, releasing the “Global Strategy for Containment of Antimicrobial Resistance” report, which documented the health effects of AMR and explored its possible implications on the broader economy. ¹⁷ More action followed in 2002, when the European Union Council released a recommendation for prudent use of human antimicrobial drugs, followed by animal antimicrobial drugs shortly thereafter. ⁸ Subsequently, in 2006, all E.U. member states banned the use of antimicrobial agents as growth promoters in farm animals. ¹⁸

Action has been slower in many non-E.U. countries. In North America, one of the earliest measures was seen in the United States, when legislation was passed in 2008 that required drug manufacturers to begin reporting the amount of drugs with antimicrobial active ingredients they sold for use in food-producing animals to the U.S. Food and Drug Administration (FDA) on an annual basis. ¹⁹ While this was a positive step, because antimicrobial surveillance is an important measure that is necessary to combatting AMR, if change is to occur, this measure needs to be supplemented with policies that limit excessive sales. However, a policy of this nature was not issued in the United States until 2015, when the FDA introduced the Veterinary Feed Directive final rule, which outlined a veterinarian’s responsibilities pertaining to authorizing the use of antimicrobials in animal feed. ¹⁹

Gradually, more countries started to strategize the development of national action plans for containing AMR, with some establishing national surveillance systems. Nevertheless, work still needs to be done to ensure that data is comparable across national surveillance systems, as antimicrobial use and resistance data is currently unreliable in many developing and developed nations. ²⁰ In fact, some countries rely on third-party companies to produce data regarding comprehensive, population-level antimicrobial prescription trends, and real-time laboratory surveillance on AMR is lacking. ²⁰

In 2015, the WHO released a global action plan (GAP) for addressing AMR, and in 2016 all United Nations member states agreed to develop national action plans in accordance with the GAP. ⁴ Overall, the GAP focuses on 5 objectives:

education initiatives to raise awareness and understanding of AMR

Since 2017, regulatory action has been emerging in North America, as evidenced by increased antimicrobial oversight in agriculture and agri-food sectors in Canada and some U.S. states from 2017 onward.^20,21

National Differences: Pharmaceutical Industries

The rise in prominence of AMR in many cases is related to the profit-driven tactics of major pharmaceutical companies. It is important to note that in 1945, the same year that pharmaceutical companies began widely distributing penicillin, Alexander Fleming cautioned against imprudent use of antimicrobials because of the potential of encouraging AMR.^8,17,27 Therefore, the concept that microbes, particularly bacteria, could become resistant to previously effective antimicrobial drugs is not new; rather, it was introduced in the early days of antibiotic commercialization.

Angus ¹⁵ documents how many pharmaceutical companies enthusiastically entered the untapped antibiotic business, beginning with the initial commercialization of penicillin and continuing with the discovery and use of many other antibiotic compounds. As the number of drug companies investing in antibiotic development grew, the price of unpatented drugs, such as penicillin, declined.^15,28–30 Drug companies responded by promoting the use of penicillin in everything: not just for treating bacterial infections, but also for use by healthy individuals to keep everyday germs away.^15,31 With no prescription required for antibiotics in the United States until the 1950s – and much later, if at all, in other countries – penicillin was easily available.^{15,27,32–34}

Manufacturers also made throat lozenges, gum, toothpaste, and even cosmetic products containing penicillin.^15,31 New bactericidal agents were immediately patented post-discovery, enabling pharmaceutical companies to market them at higher prices than penicillin. This unquenching desire for profit from the pharmaceutical sector supported the production of as many antibiotics as possible, regardless of need.

In the 1960s, national markets were saturated with unnecessary drugs, with many new drugs being fixed-dose combinations of 2 or more existing antibiotics, despite little evidence to suggest their increased effectiveness.^15,35,36 Simultaneously, there was a push from pharmaceutical industries for the development and use of broad-spectrum antibiotics, which treat multiple bacterial infections, rather than narrow-spectrum drugs, which kill only target bacterial species.^15,17,29 These trends continued until the antibiotic development pipeline dried up in the 1980s, with few new antibiotic classes being discovered in the past 30 years.^5,8 Consequently, pharmaceutical industries shifted their priorities to drugs more profitable than antibiotics, ⁸ as a result of antibiotic drugs being hard to develop and useful for only a limited period post-market due to drug resistance. ⁵ This left most countries with a dwindling supply of effective antibiotics, as almost all novel antibiotics since the 1970s have been modified versions of existing agents. ¹

The Nordic Scene

Remarkably, Nordic European countries did not follow the 20th-century antibiotic production trends that existed in most other developed countries.^26,37 Instead, Scandinavian drug regulatory systems required that drugs be authorized for marketing prior to being available for purchase as early as 1928 in Norway and 1935 in Sweden.^26,37 To minimize the number of useless or substandard drugs entering the market as a result of misleading claims from manufacturers, only “medically justified” drugs were approved in these Nordic countries. ²⁶ By contrast, drug regulatory initiatives were first federally implemented in the 1960s in most other developed countries, requiring new drugs to be proven effective and safe prior to market approval from then onward.^26,29 In 1938, Norway revised its drug laws to ensure that new drugs were not only medically justified, but also “needed,” meaning that new drugs needed to be more effective than existing drugs for the same purpose or, alternatively, able to provide the same therapeutic benefit in an ameliorated way (i.e., at a lower cost). ²⁶ As a result of this ideologically different approach to drug development in Nordic countries compared to the rest of the world, significantly fewer antibiotic drugs were approved. For example, in some Scandinavian countries, certain penicillin drugs were determined as having the potential of provoking unnecessary use and thus were not approved. ³⁷ In Norway, combination drugs were regarded with skepticism and considered to be superfluous and, therefore, rarely made it to market. ²⁶ Similarly, broad-spectrum antibiotics were frequently deemed unnecessary, not being found to have significant advantages over existing drugs; hence, narrow-spectrum drugs remain much more widely used in the country to this day. ²⁶ Clearly, the central goal in many Nordic countries was to prioritize human health by limiting the production of drugs that did not provide a new benefit to the public, rather than to maximize profit.

The benefit of the Nordic model of pharmaceutical development is starkly evident when analyzing AMR trends today, as Nordic countries have among the lowest rates of AMR worldwide and antibiotics are consumed in Scandinavian countries half as often as in other developed countries.^24,38 For example, data from the Organisation for Economic Co-operation and Development (OECD) show that the average proportion of resistance for 8 priority pathogen-antibiotic pairs were 5.6, 5.5, and 3.5 in Sweden, Norway, and Iceland, respectively, while the OECD average for the same 8 pairs was 17.4 in 2015.³⁸ Regarding antibiotic consumption, data from 2015 indicates that 5,666 DDDs were used per 1,000 people in Norway; however, 10,298 DDDs were used per 1,000 people in the United States. ²⁴ Such data support that the stricter developmental measures imposed in Nordic countries during the antibiotic discovery era of the 1940s to the 1970s have allowed the smaller number of approved drugs in these countries to remain effective for longer. By contrast, the market-driven incentives to drug development employed in most other developed countries significantly accelerated AMR through marketing strategies that promoted the perverse use of antibiotics and through the market influx of new antibiotics that were not clinically superior to existing ones. The lesson here is that social democratic countries, such as Scandinavian countries, tend to not simply see drugs as commodities, but rather as therapeutic agents for public health. This perspective has allowed them to develop antibiotics sustainably, thereby benefiting their entire nations, rather than only benefiting the pharmaceutical industry and those with vested interests in it.

National Differences: Neoliberalism, Commodification Levels, and Antimicrobial Resistance

The commodification of services to meet capitalist political agendas has not been limited to pharmaceutical industries; in fact, many countries have historically commodified important services such as health care, childcare, and education and continue this practice today. Commodified services contribute to expanding private health sectors, effectively dividing populations based on socioeconomic status and consequently increasing national health inequalities. ¹¹ This effect has been particularly observed as a side effect of economic globalization coupled with the rise of neoliberal ideologies, with neoliberal state theory supporting free markets, free trade, and the individual right to freedom of choice over state interventions and governance by majority rule. ³⁹ Neoliberal values are influencing countries to minimize state involvement by reducing governmental spending and social programs.^11,40 As a result, global income inequalities have been on the rise since the 1980s, with the richest 1% owning 45% of the world’s wealth. ⁴¹ In developing countries, income inequalities increased by 11% from 1990 to 2010, largely because of globalization processes such as international trade agreements. ⁴² Increased income inequalities are strongly correlated with increased non-income inequalities, reflected by a greater chance for disease among low-income populations as a result of inaccessible health services.^11,42

When considering these economic trends in relation to AMR, neoliberalism likely provides the underlying ideology influencing governments’ limited or counter-productive role in putting forward actions that effectively control AMR. Data indicate that developed countries with greater levels of income and non-income inequalities also tend to have higher levels of antimicrobial-resistant bacteria. ⁴³ This is demonstrated by recent data trends on AMR in developed countries, specifically the OCED countries rated highest for their provision of public goods (i.e., Denmark, Norway, and Sweden) compared to those ranked the lowest (i.e., United States, Ireland, and Australia). ⁴⁴ The IQVIA MIDAS database shows that the percentages of drug-resistant Escherichia coli isolates are significantly higher for lower-ranked countries compared to the top countries for bacteria resistant to aminopenicillins, third-generation cephalosporins, and aminoglycosides, among other antibiotics. ²⁴ This trend suggests that the neoliberal ideology has had a negative effect concerning AMR on the countries most influenced by it, as this ideology presumes that commodifiable, product-based solutions can fix any problem ³⁹ – however, in the case of AMR, this mentality has caused the saturation of the market with unproductive replicas of existing antibiotics and historically encouraged the excessive use of newer – but not necessarily better – antibiotics. Interestingly, while this fetish for product-based solutions represents neoliberalist values, it traces its roots as far back as the late 19th century, when the germ theory of disease sparked interest in “magic bullet” laboratory solutions to diseases. ⁴⁵

Furthermore, the positive relationship between rates of inequalities and drug resistance may be explained by the fact that disadvantaged people within a population are at an increased risk of acquiring infectious diseases, among other health problems. ⁴³ As such, within highly inequitable countries, wealthy individuals also have higher incidences of infectious disease compared to those in more equitable countries, due to the communicable nature of these diseases. ⁴³

Within developing countries, the loans and debt relief solutions provided by international financial institutions, such as the International Monetary Fund and the World Bank, are often conditional upon the nation’s uptake of neoliberal policies. ⁴⁶ With many of the world’s poorest countries receiving adjustment loans with such conditions, numerous low- and middle- income countries (LMICs) have introduced neoliberal policies that promote free markets and increase privatization.^12,46 Connecting this to AMR, trends indicate that national AMR rates are positively associated with a higher percentage of private health care. ⁴⁷ Besides the negative effect that privatizing essential services has on health care access, this correlation also arises from the fact that the private sector tends to be less regulated than the public sector, and therefore the quality of received care and prescription practices may vary from one private clinic to another. ⁴⁷ Furthermore, health workers at private clinics are more likely to be influenced by pharmaceutical companies to overprescribe certain drugs. ² Additionally, while antimicrobial consumption in developing countries has increased dramatically in recent years, many LMICs still lack access to crucial antimicrobial drugs. ¹⁰ Low governmental expenditures on health services within LMICs are an important barrier contributing to the persistence of the problem of inequitable access to antibiotics. ⁴⁸ Public health clinics tend to have a limited drug inventory, and while private health clinics may have more options, the drugs are sold at high prices that many cannot afford. ⁴⁸

Given the evidence of the negative impacts of neoliberal ideologies within both developing and developed countries, rising AMR rates need to be mitigated through systemic changes. Health care services and antimicrobials must cease to be viewed primarily as commodities, but rather as necessities to which no individual should be denied access as a result of socioeconomic status. Protecting those most vulnerable to infectious disease will, by extension, also protect more advantaged individuals from contracting that infection, thereby decreasing AMR within that population.

National Differences: Antimicrobial Resistance Action Strategies

Wide national differences in approach exist in addressing the AMR public health threat through the prioritization of this issue. Table 1 highlights the differences in the national AMR plan, antimicrobial use, and resistance reports in Canada to equivalent documents in Sweden, one of the countries with the lowest levels of antimicrobial use and resistance in the world.

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Table 1.

National Differences in Antimicrobial Resistance Action Plans in Canada Versus Sweden.

Category	Canada	Sweden
Rate of prescription (per 1,000 inhabitants)	Min: 358 (the territories)Max: 970 (British Columbia)	296
Narrow-spectrum antimicrobial use	Not mentioned	Increased
Broad-spectrum antimicrobial use	Not mentioned	Decreased
Animal antimicrobial use (Kg for sale/year)	950,000 (total livestock a : 26.7 million)	10,042 (total livestock a : 3.2 million)
Antimicrobials as animal growth promoters	Yes	Banned since 1986
Environmental considerations	No focus on impact of antimicrobial residues on the environment and AMR	Revising manufacturing practices to ensure minimal antimicrobial residues in the environment

^aTotal livestock = the closest and most recent estimate of total population of cattle, sheep, and swine in each country.

In Sweden, the national average of antibiotic prescription is the lowest ever, with 296 prescriptions per 1,000 inhabitants as of 2018.⁴⁹ In Canada, the rate of prescription varies depending on the province or territory, with the lowest rate – 358 prescriptions per 1,000 inhabitants – in territories and as high as 970 prescriptions per 1,000 inhabitants in British Columbia. ⁵⁰ Major differences in animal antimicrobial use also exist: In Canada, more than 11 times more antimicrobials by weight were sold for use in farm animals in Canada compared to Sweden in 2017.^49–52 Furthermore, in Sweden, sales of broad-spectrum antimicrobials are decreasing for both human and animal use, and narrow-spectrum antimicrobial sales are increasing; in Canada, there is no mention of “narrow-spectrum” antimicrobials in either of the 2 Canadian reports, suggesting that transitioning to narrow-spectrum antibiotics is not a priority for Canadian officials.^49,50 Research supports that narrow-spectrum antimicrobials slow down the horizontal-transfer of AMR, as they only target specific, disease-causing bacteria.^15,17 Also, the WHO classifies certain antimicrobials, specifically third-generation cephalosporins, fluoroquinolones, and polymyxins, as “highly prioritised critically important antimicrobials” for human health. ⁴⁹ Sweden has responded to this announcement by reducing sales for the 3 aforementioned antimicrobials for use in production animals by 92%, 82%, and 66%, respectively, since 2009.⁴⁹ Meanwhile, the Canadian report does not specify whether sales for these compounds have been reduced and, if so, by how much; however, it does mention that between 19% and 32% of farmers reported no use of “medically important antimicrobials.” ⁵⁰

In Sweden, the use of antimicrobials as animal growth promoters has been banned since 1986, while antimicrobials continue to be used for this purpose in Canada.^49,50 However, as of 2018, a Canadian policy went into effect that no longer allows medically important antimicrobials sold for food-producing animals to have growth-promotion claims, which is the right step forward. ⁵³

Lastly, the Canadian AMR framework lacks focus on the environmental impacts of antimicrobial residues and on raising awareness of how antimicrobials in the environment contribute to AMR. ⁵⁰ By contrast, the Swedish action plan considers the environment a priority and is thereby calling for the development of rules on good manufacturing practice to minimize the dumping of antimicrobials into the environment. ⁴⁹

Overall, there are significant differences between the priorities of the Swedish versus the Canadian national strategies for addressing AMR. Canada demonstrates fewer antimicrobial regulations – especially regarding antimicrobial use in animals – which may have contributed to the rise in AMR in Canada compared to Sweden.