In 2019, the World Health Organization (WHO) listed antimicrobial resistance (AMR) as one of the top ten threats to global health, due to the catastrophic impact it has the potential to cause.1 The Review on Antimicrobial Resistance estimated that inaction in addressing AMR could result in an estimated 10 million deaths per year by 2050, and yield a much greater economic impact than that of the 2008–2009 financial crisis.2 With the onset of the current COVID-19 pandemic, there has been a growing urgency towards further investigating issues of resistance in the light of the spread of the novel infectious disease.
Antimicrobial resistance (AMR) occurs when pathogens (bacteria, viruses, fungi and parasites) develop a resistance or tolerance to the medicines that are used to combat these microorganisms, such that these treatments are no longer effective.3 Although AMR is a natural phenomenon, the speed at which it occurs is impacted by how much exposure pathogens have to treatments. There have been numerous publicised cases of pathogens developing AMR, including methicillin-resistant Staphylococcus aureus (MRSA), drug-resistant tuberculosis and antibiotic-resistant gonorrhoea,4,5 which are all far more harmful strains than the original pathogens.
AMR has been increasing in low-, middle- and high-income countries around the world in recent years, and this trend is expected to continue.5–7 Klein et al. (2018) conducted a trend analysis on antibiotic consumption between 2005 and 2015 in 76 countries.8 The results indicate that between this time period, antibiotic consumption rose globally by 65% (measured by defined daily doses [DDD], a standard drug intake metric), primarily driven by increases in consumption in low-and middle-income countries (LMICs); estimates suggest a 77% increase in antibiotic consumption rate per 1,000 inhabitants in these regions. Projecting global consumption patterns in 2030 with no policy interventions, the study estimated a 200% increase. This increase has been principally driven by increase in global demand for antibiotics, which are overused and, in many cases, misused (e.g. the use of antibiotics for common viral infections, like the flu, in humans and as growth promoters in farm animals) and compounded by falling investment in the development of new antimicrobial agents.9 The indiscriminate use of antibiotics in the animal farming sector, where healthy animals are given antibiotics as a precaution, is just part of what makes the livestock industry responsible for an estimated 70–80% of the global total of antibiotic consumption.10 However, antibiotics have undoubtedly been overused by humans and in agriculture practices (both livestock and crop farming).1,11 These drivers respond to economic incentives as seen in physician-patient relationships, farming practices for greater yields as well as other environmental factors. While these drivers are not unique to LMICs, their impacts can be felt more severely in these regions due to a lack of regulation and other socio-economic factors.
Interventions need to consider the multisectoral nature of AMR if it is to be controlled as a public health threat, using a One Health approach which recognises the links between antimicrobial use in humans, animals and the environment.11 The WHO’s 2015 Global Action Plan on AMR identified several key methods for reducing AMR as a threat, including through: 1) optimisation of the use of antimicrobials in both human and animal health; 2) reducing infections, through effective sanitation, hygiene and other infection prevention measures; 3) sustainable investment in the development of new antimicrobials, diagnostic tools and other interventions.12 Using this framework, over the last few years, many countries have attempted to improve their data collection systems and formulate interventions and policy measures to address AMR, primarily through their own domestic policies but also by contributing to the global policy landscape. National AMR Plans, in line with the WHO framework detailing country-specific interventions have been drawn up and operationalised in many countries.12 However, many of these initiatives have little to no evidence concerning their relative costs and benefits; an issue of significant importance, particularly for resource-constrained settings such as LMICs which face multiple demands on their budgets.
The Global Action Plan on AMR also emphasises the need to bridge the existing gap in economic research to support improved AMR awareness (objective 1) as well as the urgency of ensuring an economic-evidence based use of interventions to feed into the development of a financial case for investment in AMR diagnostics and treatments (objective 5).11 LMIC governments face many competing interests for new health investments, and there has been an increasing focus on using economic evaluation and health technology assessment (HTA) to inform resource allocation decisions in healthcare and maximise the value for money of the health system overall.13 Economic analysis on interventions to address AMR is a necessary part of the required evidence base for justifying government expenditure and investment in interventions of this type, and therefore is a key step in AMR prevention and control. LMICs have developed growing capacity to conduct health economic evaluations in recent years,14 yet the most recent systematic review on the cost-effectiveness of measures to contain the occurrence of AMR dates back to 2002.15 This study highlighted that inadequate evidence was available on this subject of economics for AMR interventions and more investigation was required. Since then, little has been done to improve available evidence.
In order to bridge this important evidence gap and contribute to the objectives outlined by the WHO Global Action Plan on the important evidence needs in the realm of economics of AMR, this systematic review aims to detail data from economic evaluations regarding the value-for- money of these interventions as a step towards optimising resource use in tackling AMR. In specific, this review will answer the following questions:
What interventions to address antimicrobial resistance have been the subject of an economic evaluation?
In what types of setting (e.g. high-income, low-income, regions etc.) have these economic evaluations been focused?
Which interventions have been estimated to be cost-effective, and has this result been replicated in other settings/contexts?
What economic evaluation methods or techniques have been used to evaluate these interventions?
What kind of data has been used in conducting economic evaluations for these interventions? What is the quality of this data?