Reducing the Ethical Burdens of Antimicrobial Stewardship using a Social Determinants Approach

Abstract

Antimicrobial resistance is an emerging global health problem. Antimicrobial stewardship interventions attempt at regulating the prescription and use of antimicrobials so that the emergence of resistance is reduced. But antimicrobial stewardship interventions have several ethical issues such as inequity in access to antimicrobials among the poor who need them more, and limitation of the autonomy of prescribers and patients. Several upstream social determinants influence susceptibility to infections, antimicrobial prescription practices, and emergence of antimicrobial resistance. Some of these social determinants impose ethical burdens on the antimicrobial stewardship interventions. Addressing these social determinants with a public health approach will help reduce antimicrobial resistance. This article argues that the social determinants approach helps reduce the ethical burdens of antimicrobial stewardship.

Introduction

Antimicrobials are the most important innovations in the last century, which have contributed to substantial reduction in morbidity and mortality globally (Centers for Disease Control and Prevention 2020). However, Alexander Fleming, the person who discovered the first antibiotic, penicillin, himself hinted about the possibility of microbes developing resistance to penicillin (Aminov 2010). Now, about three quarters of a century later, his prediction has not only come true, but has grown into a major public health problem. Antimicrobial resistance is the loss of the effectiveness of antimicrobials in killing or inactivating the microbes that it once acted against (Yoshikawa 2002). There are several mechanisms of development of antimicrobial resistance which happen through genetic mutations that take place in the microbe due to selection pressures, or these mutations are transmitted horizontally through transmissible genetic elements from other related microbes (Jindal et al. 2015).

One of the most important determinants of emergence of antimicrobial resistance is indiscriminate and irrational use of antimicrobials. Therefore, the World Health Organization adopted the Global Action Plan on Antimicrobial Resistance in 2015, in which it laid emphasis on various measures to reduce antimicrobial resistance, the most important of which was implementation of the Antimicrobial Stewardship Program (AMSP) in all member countries (World Health Organization 2015). The word stewardship means the responsible planning and management of a scarce resource such that it is protected and preserved against misuse and retains its ability to benefit people at large. The goals of AMSP are to optimize the prescription of antibiotics, promote behavior change in prescription and dispensing practices, improve quality of care and patient outcomes, reduce unnecessary health care costs, reduce emergence of antimicrobial resistance, prolong the life span of antimicrobials, limit adverse economic impact of antimicrobial resistance, and to promote rational use of antimicrobials (World Health Organization 2019).

One of the major arguments supporting the need for antimicrobial stewardship is that we need to protect antimicrobials for the future (File et al. 2011). We need to protect the world from the impending “post-antibiotic era,” which refers to the cataclysmic time when there will not be any antimicrobials left to fight infections. However, in critical illness situations, starting a patient on antibiotics immediately may be a major life or death decision. This raises a major ethical issue of inadvertently restricting access to life-saving antimicrobials to the people who are alive today, to save antimicrobials for people of tomorrow. It is an ethical conflict between the suffering of people of today versus an abstract imaginary suffering of people of tomorrow (Abimbola et al. 2021).

Development of resistance has become a routine phenomenon for most antimicrobials. Therefore, the question arises whether restricting its use will do any good. Should the health system rather focus on investing in preventing infections and research and development of newer antimicrobials? The problem with this seems to be that the shelf life of an antimicrobial is rather short because of the problem of antimicrobial resistance. Therefore, pharmaceutical companies who are in the business driven by profit hesitate to invest in antimicrobials which will give them profits only for a short period, compared to drugs for chronic diseases which will keep the cash registers ringing for longer (Razzaque 2021).

The Global Charter for Public Health applied to the AMR problem has described that comprehensive health and wellbeing of humans, plants, and animals is an essential requirement to address the global AMR problem. Communicable diseases must be controlled through a thorough One Health approach by applying stringent environmental measures. The World Federation of Public Health Associations called for mainstreaming public health at the core of all antimicrobial policies to control AMR (Lomazzi et al. 2019). The World Health Organization in its technical series on primary health care declared that “antibiotics are often used as a substitute for basic public health” and emphasized that the important approach to tackling the problem of AMR is provision of basic primary health care (World Health Organization 2018). However, these initiatives did not address the ethical advantages of using a social determinant and public health approach to the problem of AMR.

This commentary proposes adopting a public health approach to preventing antimicrobial resistance, considering social determinants of antimicrobial requirement, prescription, and resistance, and addressing these social determinants as a strategy of antimicrobial stewardship. The article argues that addressing these upstream determinants of infections, antimicrobial use and antimicrobial resistance will work in a sustainable manner to limit the antimicrobial resistance problem while overcoming some of the major ethical burdens associated with stewardship. The arguments in this article are applicable to a typical low- and middle-income country setting where there is growing antimicrobial resistance as well as a high demand for antimicrobials due to the burden of communicable diseases.

Social Determinants of Antimicrobial Requirement, Prescription, and Resistance

The World Health Organization framework of social determinants of health proposes economic stability, education, gender, environment, livelihood, food, and nutrition as some of the key social determinants that influence susceptibility to infections and requirement of antimicrobials (CSDH 2008). Persons who are underprivileged on one or more of these intersecting social axes contract more infections, and therefore require more antimicrobials. For example, a woman living in a crowded urban low-income settlement, with poor access to clean water and sanitation and poor access to health care services, may develop several episodes of urinary tract infections for which she may require antimicrobials. She may not have access to a public health facility nearby where she can get treatment for this condition and may rely on unregistered practitioners and over-the-counter use of antimicrobials in inappropriate dose, frequency, and duration. She may travel a long distance to reach a primary care facility after a few bouts of infection and there the implementation of antimicrobial stewardship program may restrict the availability of higher antimicrobials, which she may require due to resistance to lower ones. The facility may also lack the microbiology laboratory facility for a proper culture and sensitivity result. This woman may continue to have repeated infections as the upstream determinants of her susceptibility to infections; requirement of antimicrobials is not addressed and the AMSP does not consider the inequities introduced due to gender, poverty, and environmental conditions. In summary, the following sections will delve into these upstream social determinants of susceptibility to infections, requirement and access to antimicrobials, and the ethical burdens introduced by them.

Social Determinants of Infection Susceptibility

The social context in which people live including the social power structures, hierarchies, environmental conditions influence their health and wellbeing (Braveman et al. 2011). Poverty and food insecurity lead to poor nutrition and suppressed immunity. Unhealthy environmental conditions such as unsafe water, polluted air, and lack of sanitary facilities increase exposure to infections. Such unhealthy environments also increase vector breeding and increase risk of vector-borne diseases. Housing and living conditions can lead to over-crowding which increases transmission of air-borne diseases like tuberculosis. Illiteracy and lack of awareness reduce uptake of health promotion and disease prevention measures. Social power hierarchies such as gender, religion, caste, and class further distance people from the health system and push people out of disease-preventive and health-promotive safety nets (Semenza 2010).

Social Determinants of Antimicrobial Prescription Practices

Lack of access to skilled and licensed medical practitioners is a common phenomenon in many parts of the country. Many patients with infectious conditions resort to seeking health care from unregistered practitioners and taking medications from the pharmacy over the counter without a prescription. Often, antimicrobials are misused in these contexts (Bloom et al. 2017). Doctors’ prescription practices are influenced by social factors in the health system. Pressures from pharmaceutical marketing practices, from patients demands, and insecurities associated with potential litigation force physicians to over-prescribe antimicrobials in the private sector (Aiello et al. 2006). On the other hand, antimicrobials are largely inaccessible to the poor in the public sector (Laxminarayan et al. 2016). This inequity in prescription and access of antimicrobials is a major ethical consideration. Another major ethical issue in implementing antimicrobial stewardship policies is that these interventions compromise the autonomy of the prescriber (Yen and Cutrell 2021). This is particularly problematic where the clinical diagnosis is not very clear. Standard treatment guidelines work well only when the clinical diagnosis is clear. Such situations of uncertainty are extremely common in clinical medicine, and this demands intuitive judgment calls on the part of the prescriber. Many prescribers find it unacceptable to have their clinical authority challenged and restricted in these situations. The prescribers feel that their autonomy and intellectual agency is compromised by having their antimicrobial prescriptions reviewed, critiqued, and revised.

Social Hierarchies and Inequities Impact Antimicrobial Stewardship Programs

Good-quality antimicrobials that are effective against common microbes that cause disease are a common good. The availability of such antimicrobials ensures that lives can be saved and quality of life improved. However, excessive use of such an antimicrobial leads to development of antimicrobial resistance. Antimicrobial stewardship initiatives regulate the use of antimicrobials to preserve their effectiveness. Restricting the use of antimicrobials makes them less accessible to certain vulnerable sections of the society like the economically backward compared to the affluent. The poor may be the ones who require the antimicrobials more as they are more susceptible to infections. So, to protect the interests of a few people who can afford the antimicrobials, restricting the use of antimicrobials, may end up harming the interests of the poor and vulnerable who may need it more. Thus, there is an issue of balance between individual benefit versus common good and the issue of imbalance between who benefits and who gets harmed by implementing antimicrobial stewardship (Abimbola et al. 2021).

As one of the antimicrobial stewardship initiatives, the World Health Organization proposes classifying antimicrobials into three categories, namely Access, Watch, and Reserve (AWaRe) (Adekoya et al. 2021). The Access group of antimicrobials are those which act against common microbes causing diseases and they are relatively narrow spectrum antimicrobials. They are slated for liberal and free access. The Watch group of antimicrobials are relatively broader spectrum and are classified for use only under specific conditions. The Reserve group is the one which is a very broad spectrum, exclusive group of antimicrobials reserved for the extreme cases of multidrug-resistant organisms. The Access antimicrobials such as amoxycillin, ciprofloxacin, and metronidazole are used liberally; they slowly become less effective as selection pressure creates microbes which are resistant to these antimicrobials. This leaves only the Watch group of antimicrobials as drugs of choice for infections. However, the access to these antimicrobials such as third-generation cephalosporins is restricted. In a typical public health facility run by the government, the most readily available drugs are the Access group of antimicrobials and sometimes these antibiotics may not be sufficient for a particular clinical situation. These facilities do not have adequate stock of Watch antimicrobials, thus putting the poor and vulnerable people who access these public health facilities at a disproportionately high risk compared to the rich and fortunate who can purchase Watch category of antimicrobials for a price.

Addressing Upstream Determinants is the Ethical Option for Preventing Antimicrobial Resistance

Working towards achieving the Sustainable Development Goals (SDGs) will ensure that the upstream social determinants of susceptibility to infections, antimicrobial prescription practices, and the social inequities that make antimicrobial stewardship interventions burdensome are addressed (Gajdács et al. 2021). The Global Action Plan on Antimicrobial Resistance adopted by the World Health Organization in 2015 has five main objectives, namely (World Health Organization 2015):

• i.Improve awareness and understanding of antimicrobial resistance through effective communication, education, and training.
• ii.Strengthen the knowledge and evidence base through surveillance and research
• iii.Reduce the incidence of infection through effective sanitation, hygiene, and infection prevention measures
• iv.Optimize the use of antimicrobials in human and animal health
• v.Develop the economic case for sustainable investment that takes account of the need of all countries, and increase investment in new medicines, diagnostic tools, vaccines, and other interventions.

Antimicrobial stewardship addresses the fourth objective. It tries to protect and preserve the existing antimicrobials so that a “post antibiotic” era is prevented. However, there are significant ethical burdens of antimicrobial stewardship. These have been described in the preceding sections on social inequities associated with the antimicrobial stewardship interventions. Objective number three, which focuses on infection prevention and control, depends on vaccination and addressing important environmental and social determinants of health.

Improving living conditions by providing access to safe drinking water, clear air, good sanitation facilities can lead to reduced chance of infections. Universal Health Care (UHC) is achieved through comprehensive primary health care (PHC) including good coverage of immunization, access to social determinants of health, access to primary care doctors and health care providers, and microbiology laboratory services to provide timely diagnostic backup can all significantly reduce the emergence of antimicrobial resistance (Bhatia 2018). This is a common good and can effectively combat antimicrobial resistance without imposing any restrictions on the access to antimicrobials to those who need them the most.

Any stewardship intervention must be built based on trust. Trust builds through perception of genuine intentions and transparency. Hospitals and health facilities must work towards fostering patients’ trust. Prescribers and patients will buy into stewardship interventions if they trust the interventions. When prescribers and patients trust the system and buy into the antimicrobial stewardship, it will substantially minimize the ethical burden. Therefore, the stewardship intervention must be transparent, must be flexible and allow deviations to the protocol on a case-to-case basis, and must be seen by both prescribers and patients as being supportive and positive.

Adopting a social determinants approach focuses on providing a healthy environment and positive social determinants. When this is combined with a planetary health approach where health is defined not just keeping humans at the center, but keeping all the world including animals, plants, trees, water, air, and the environment as the focus, then it looks for creating sustainability. It focuses on building nutrition, immunity, and planetary co-existence rather than just protecting antimicrobials (Abimbola et al. 2021).

Conclusion

To prevent the emergence of antimicrobial resistance, antimicrobial stewardship initiatives are implemented, where use of antibiotics is restricted so that they are not misused. This poses inequitable ethical burdens on the weaker sections of the society. An alternative approach to this problem of emerging antimicrobial resistance is the social determinants approach, in which social determinants of infection susceptibility, antimicrobial prescription, and the social inequities imposed by the antimicrobial stewardship practices are addressed. This approach is ethically more justifiable as it creates an overall positive development and reduces the number of restrictions posed on people.

Author Contribution

The single author conceptualized, drafted, and edited the manuscript.

Funding

This manuscript contains insights gained while conducting an operations research project to assess the appropriateness of antimicrobial use in public health facilities funded by the Tamil Nadu Health Systems Reforms Program (TNHSRP), the fund administered by the Indian Institute of Technology – Madras. The grant was received by Vijayaprasad Gopichandran.

Tamil Nadu Health Systems Reforms Program

Declarations

Ethics Approval

As this manuscript does not report any research on human or animal participants, no ethics review or approval was obtained.

Consent to Publish

Not applicable.

Competing Interests

The author declares no competing interests.