Antimicrobial resistance (AMR) is a global threat that claims 700 000 lives every
year. If no urgent actions are taken, by 2050, AMR will cause an estimated loss of
10 million lives and $US100 trillion.1 Over the years, commonly identified infectious
agents have developed resistance to antimicrobials. Since the discovery of penicillin
in 1928, 20 000 potential resistant genes of nearly 400 different types have been
identified.2 Methicillin-resistant Staphylococcus aureus alone causes more than 80 000
severe infections and claims more than 11 000 lives each year.3 The World Bank estimates
a reduction in global domestic product per annum of 1.1%–3.8% by 2050 if AMR remains
unchecked, and that an investment of US$9 billion per year will be required to counteract
the problem.4
AMR affects all countries, but the burden is disproportionately higher in low-income
and middle-income countries.1 To halt the spread of AMR, it is important to understand
what contributes to its emergence. While the overuse of antimicrobials in both humans
and animals is broadly implicated and strategies are developed to counteract such
an overuse, the broader factors that contribute to AMR are often overlooked. In addition,
national action plans on AMR are often constrained by lack of comprehensive multisectoral
and multipronged approaches (eg, too focused on the health sector), and their findings
are only relevant for a limited period of time as AMR continues to evolve at a fast
pace.5 A recent assessment of country situational analyses against the political,
economic, sociological, technological, ecological, legislative, and industry (PESTELI)
framework identified important gaps in addressing AMR.6
Indeed, collaborative efforts are necessary to delineate global, regional and local
contingency plans for AMR. A multitude of factors contribute to the development of
AMR. Many of these factors transcend discipline and sectors. Efforts to counteract
AMR through a traditional biomedical approach alone may fail to curb the current challenges.
In this editorial, we draw insight from some recent papers in BMJ Global Health on
AMR, and we use the PESTELI framework to highlight the multifaceted challenges involved
in tackling AMR in low-income and middle-income countries, and the need for a holistic
and multisectoral approach.
Political factors
Weak governance often leads to lack of attention to health system functioning and,
hence, to weakened regulations for the antimicrobial stewardship. Poor antimicrobial
stewardship and inappropriate antimicrobial use often in substandard doses challenge
the efforts to contain the emergence and spread of AMR.7 In addition, budgetary constraints
limit the prioritisation for surveillance of AMR.8 Improved surveillance systems and
surveillance data, for example, through establishing computerised data repository,
are necessary to inform policies and to respond to both the emerging threats and the
long-term trends in resistance.9 However, existing surveillance systems to monitor
antimicrobial consumption in both humans and animals and to identify the rate and
trends in development of resistance are often inadequate.8 Strong political commitment
with multistakeholder engagement to strengthen surveillance networks and AMR reporting,
and stewardship are essential.
The lack of infrastructure due to poor economy, corruption and low preparedness in
many low-income and middle-income countries has led to inadequate attention to preventive
measures, such as water, sanitation and hygiene, leading to high burden of infectious
diseases. Often in such settings, antimicrobials function as a ‘quick-fix’ infrastructure,
used in place of and to rescue the fractured infrastructures of care, water, sanitation
and hygiene.10 Universal access to water and sanitation alone is expected to lead
to a 60% reduction in diarrhoeal illnesses treated with antimicrobials. Maintaining
hygiene through hand washing alone by clinicians in healthcare settings can decrease
the infectious diseases and the use of antimicrobials by 40%.11 The political awareness
and prioritisation of these simple yet highly effective preventive measures remain
low; hence, they remain inadequately addressed.
Economic factors
As health systems in low-income and middle-income countries often lack resources (functional
and infrastructural) to reach a large population, more so in rural areas, universal
access to primary healthcare services becomes a major challenge.8 Access to appropriate
antimicrobials against common infections is imperative to save lives.12 However, because
regulatory mechanisms are weak, antimicrobials are often used inappropriately and
irresponsibly. The struggle between ensuring universal health coverage and at the
same time preserving the currently available antimicrobials is a major concern in
low-income and middle-income countries.13 In rural and under-resourced settings of
many low-income and middle-income countries, where access to qualified healthcare
workers is severely constrained, universal health coverage has been erroneously equated
with the availability of antimicrobials.10 Such a quick fix for the weak health systems
further exacerbates the inappropriate antimicrobial use. Moreover, in settings where
access to high-quality health services at health facilities is constrained by limited
functional capacity to serve large populations,13 14 inadequate health coverage and
out-of-pocket (OOP) expenditure for healthcare, especially in the private sector,
are often catastrophic.
In Nepal, for instance, household OOP expenditure for healthcare comprises about 55.4%
of health spending, with OOP at private hospitals being up to 80% of the total expenditure
at all kinds of hospitals.15 Consequently, healthcare delivery largely depends on
informal providers, pharmacists, drug dispensers and traditional practitioners.14
Often unqualified and profit driven, these providers sell antimicrobials over the
counter (OTC) for mild to moderate illnesses, a large proportion of which are self-limiting
viral infections.16 In addition, poor pharmacovigilance and drug regulation make populations
vulnerable to counterfeit and substandard medicines. Due to weak governance entwined
with the complex socioeconomic, cultural and behavioural factors that drive healthcare
seeking, it is difficult to implement a stringent regulation to control the unregulated
OTC dispensing of antimicrobials.
Sociological factors
Poor educational status and low awareness leave populations with popular myths, cultural
practices and belief systems towards the use of medicines, especially antibiotics.16
These social factors and cultural practices, combined with poverty, further leads
people to self-medicate against common infections (another quick fix), buy medications
from unregulated drug dispensaries, visit traditional practitioners and borrow medicines
from their neighbours. Medicines obtained from traditional practitioners are often
unknown chemical agents mixed with antimicrobials in substandard doses, which also
foster AMR and delay timely treatment at allopathic health centres. Driven by the
desire to get well soon and at minimal cost (again, a quick fix), patients often demand
treatment regardless of the type of infection (bacterial or viral) and avoid necessary
investigations during consultations.7 For instance, in Kenya, patient expectations
were often felt as pressure by healthcare practitioners to prescribe antibiotics.17
Technological factors
Technological innovations in diagnostics to rapidly detect infections and AMR are
critical for both improved patient care and better surveillance.13 Peripheral health
facilities often lack laboratory facilities and skilled human resources. Diagnostics
to inform the appropriate prescription of antimicrobials are not available at the
point of care, while antimicrobials are easily accessible OTC and a wide variety of
infections are treated empirically.7 In addition, healthcare innovations through computerised
real-time reporting of data are essential for improved surveillance and action. A
robust mechanism to routinely monitor diagnostics-based use of antimicrobials through
increased reporting of infectious diseases and the prescription is essential.
Industry factors
In the absence of political, social and economic changes, especially in low-income
and middle-income countries, the rise of AMR may only be counteracted through investments
in research and development of newer drugs. The decline in stakes of pharmaceutical
industries to develop new antibiotics has dwindled in the last few decades compared
with drug development in other health conditions such as cancer.1 18 With the diminished
production of newer antibiotics and growing AMR, remaining antibiotics have become
extremely expensive and are unaffordable in many low-income and middle-income countries.7
Adding on this, pharmaceutical companies’ incentives to medical practitioners and
drug dispensers to prescribe specific antimicrobials further escalate the use and
cost of antimicrobials. Another way to curb the overuse of antimicrobials is through
the use of available vaccines against common infections to reduce the burden of resistant
infections. The use of existing pneumococcal vaccine, for instance, can reduce the
antimicrobial-resistant infections by more than half.19 However, again, such new vaccines
are not easily available and affordable in many low-income and middle-income countries
unless they are subsidised with wide coverage by health systems.
Ecological factors
AMR cannot be tackled well without an ecological approach embedded in the concept
of ‘One Health’.13 The rising commercial farming, animal husbandry, food and agricultural
products use antimicrobials in huge proportions. The use of antimicrobials have become,
paradoxically, a quick-fix economic panacea in producing standard-sized animals, fish
and crops, which overlooks the enormous economic losses due to overuse of antimicrobials.10
Around 70% of medically important antimicrobials in the the USA are sold for use in
food-producing animals.20 Such widespread antimicrobial use also echoes across Europe.21
Although the available information from many low-income and middle-income countries
is limited, empirical estimates suggest that the antimicrobial use in animal food
is very high. Use of antimicrobials in these sectors puts a huge amount of drug pressure
and accelerates the rate of emergence of AMR. Legislative mechanisms are urgently
required to contain the current trend of use of antimicrobials in food and agriculture
sectors through greater collaboration with wider stakeholders and multidisciplinary
embrace of One Health.22
Conclusion
High burden of infectious diseases, poverty, weak governance and health systems, and
low awareness in many low-income and middle-income countries remain major challenges
in the fight against AMR. Efforts to address AMR globally must take into consideration
these peculiar challenges. Low-income and middle-income countries must strengthen
their health systems in ways that address these systems issues, with a focus on developing
regulatory strategies against unauthorised antimicrobial use, antimicrobial stewardship
and treatment guidelines for common infections, along with sustainable public awareness
campaigns aimed at changing health-seeking behaviour. These efforts should be based
on evidence—on each component of the PESTELI framework—tailored to the context in
each setting. Increased investment in research and development of vaccines, newer
drugs and improvement in water, sanitation and hygiene to prevent common infections,
together with the promotion of diagnostic tests to timely detect and treat infections,
are essential to curb the current trends of AMR.