4.1 New Drugs
For many decades, even where the emergence of drug resistance was recognized, much of the response (or lack thereof) by individual clinicians as well as policymakers was grounded in (apparently unfounded) confidence that new antimicrobial drugs would be discovered and developed, meaning that resistance to older drugs was of limited significance. Despite early warnings of the consequences (Holmes et al. 2016; Honigsbaum 2016) – profligate use continued and indeed accelerated in humans, animals, and agriculture. Meanwhile, the restricted use of new antimicrobials as ‘reserve’ agents – although it may help to slow the emergence of resistance – means that there are disencentives to (profit-motivated) research and development of new antimicrobials. For this and other reasons, few new antibiotic
classes or agents have been developed in recent decades (Norrby et al. 2005). Boosting more relevant research and development may thus require more public effort/funding and/or realignment of pharmaceutical companies’ incentive structures (i.e. so that profit making becomes more compatible with developing products that are most important to global public health) (Banerjee et al. 2010).
New drugs (or other means of treatment/prevention) are arguably most urgently needed for infections that have become nearly pan-resistant (e.g. extensively drug-resistant TB, or multi-resistant gram negative bacteria). Vis-à-vis other responses that target particular causal pathways (e.g. restrictions on prescriptions practices or agricultural use) they would provide a cross-cutting solution to the problem of drug resistance – i.e. addressing the problem regardless of the specific mechanisms by which it was brought about.
It is clear, however, that policymakers (and, indeed, patients) cannot rely on new drugs to ‘fix’ the problem(s) of drug resistance, since (i) the development of new antimicrobial drugs has, in recent decades, been slow and/or relatively unsuccessful, (ii) the challenges underlying difficulties with drug development have thus far proven difficult to overcome, and (iii) without other interventions to curb the increase in drug resistance, we face a never-ending problem of finding new drugs. Thus, drug resistance requires a multi-faceted and global policy response – yet one that is also tailored to the specific problems and mechanisms of resistance in a given microbe and a given context.
4.2 Research and Surveillance
Apart from finding
new treatments, other kinds of research are urgently needed, including empirical research in diagnostics, microbiology, vaccines (and other non-drug interventions), as well as social science and public health systems research (Dar et al. 2016). As a starting point, there are large gaps in our knowledge of the epidemiology of most resistant pathogens. Improving local and international public health surveillance would help to determine the impact of various resistance mechanisms and evaluate the cost-effectiveness of interventions. Yet this, in turn, requires development of cost-effective and publically acceptable surveillance mechanisms that can be more widely implemented, including in LMICs, and political and scientific agreement on which data will be collected and shared (Tacconelli et al. 2017). It also requires careful attention to the ethical conduct of public health surveillance (World Health Organisation 2017b).
4.2.1 Reducing Use in Humans
There is an urgent need to reduce antibiotic
use in human patients. The most ethically straightforward cases are those in which a person is prescribed (or purchases without prescription) an antibiotic
(with a risk of side-effects and resistance) for a condition for which it will provide no benefit (e.g. a viral illness) or where a shorter course of antibiotics is as effective as a longer course but the latter confers an increased risk of resistance and/or side-effects. In such cases, antibiotic
use constitutes a net harm to the individual and, through the risk of transmission of resistant organisms, to others.
One strategy to reduce use is to develop new diagnostics, so that patients and doctors can avoid using antibiotics where they are not required. But in the absence of perfect tests, changes in professional and public culture are also required. For example, doctors should address their own cognitive biases (see Chap. 8) as well as patient concerns about avoiding the complications of infection, and public awareness campaigns must emphasize that antibiotics are often not required and can themselves entail significant risk (to individuals and public health) (World Health Organisation 2015). International data suggest that some countries have made significant progress in reducing antibiotic
use without a significant increase in severe infections (Bronzwaer et al. 2002).
Yet, as effective antibiotics become more and more scarce, there are more difficult ethical tradeoffs to be considered, involving greater uncertainty. For example, if antibiotics become reserved for severe and/or complicated infections – so that use is banned or dramatically reduced for patients with simple infections – many patients with a simple bacterial infection (e.g. mild pneumonia) may end up being more unwell for longer, or even at a small risk of severe outcomes (even though the vast majority will ultimately recover without specific curative treatment), because they do not have access to antibiotics.
Policy to reduce use in either the low risk or the higher risk cases cannot rely entirely on individuals, since the structure of the underlying collective action problem leads to strong incentives to ‘free-ride’ on others’ reduction in use. Thus, some form of regulation is required – e.g. through antimicrobial stewardship (which has been a successful but resource intensive approach in healthcare institutions), and/or restrictions on physician prescribing. How best to design and enforce such regulation is an important matter for debate in public health ethics.
4.2.2 Reducing Use in Animals and Agriculture
As argued in later chapters of this volume (see Chaps. 7 and 18), antibiotic
use and overuse in agriculture must also be reduced. First and foremost, many have argued that the widespread use in animals of agents that are critical to human health should be dramatically reduced and/or prohibited, especially when such agents are employed for non-therapeutic purposes (e.g. as ‘growth promoters’) (Marshall and Levy 2011; World Health Organisation 2017c). But even other drugs (and non-drug agents) may lead to the co-selection of resistance determinants for critical drugs among bacteria (and fungi) shared between animals and humans. The overuse of antibiotics in agriculture in part represents a palliative for the high rates of infection in crowded ‘factory farms’, suggesting that reforming farming practices would have the dual benefits of reducing animal
cruelty and reducing drug resistant infections. Reducing or eliminating meat consumption would also obviate many of the dangers to humans of resistance in animals (although not all, since companion animals can also transmit drug-resistant infection (Guardabassi et al. 2004)). The fact that some wealthy countries have dramatically reduced or eliminated profligate antibiotic
use in farm animals (in part by giving animals more space and improving infection control practices) often at little or no long term economic
cost suggests that it is possible to minimise this driver of drug resistance (McEwen et al. 2018). Whether such practices will be successfully implemented in lower income countries remains to be seen (Dar et al. 2016).
4.2.3 Addressing Social Determinants of Health
Infectious diseases, in general, are more prevalent among poor people and communities in both high and low-income countries. Many aspects of social organization and the built environment (water and sanitation systems, health systems, etc.) alter the risk of acquiring infection, and the risk of transmission of resistance mechanisms. Historically, improvements in living conditions arguably contributed more to the decline in infectious diseases in developed/industrialised countries than discoveries of vaccines or antimicrobial treatments (McKeown 1976). One way of reducing the prevalence of drug resistant infection would be to reduce its incidence and transmission by addressing these (and other) such social determinants of health.
The rise of untreatable infections provides a new, and urgent, rationale to ensure universal access to the social conditions that enable healthy living. Even basic measures, especially if provided to all, could help minimize the transmission of resistance (e.g. by providing access to clean water and sanitation) and reduce the use of antimicrobial drugs (e.g. by providing access to high quality, and well-regulated, health systems). Since resistant infections routinely spread via international travel, wealthy nations have reasons not only to act locally but also to act globally by assisting others with less resources (see Chap. 21) – to reduce the incidence and international transmission of resistant infection (Selgelid 2008).
4.2.4 Infection Control
Infection control involves measures that aim to reduce the transmission of pathogens in an institution or community. In healthcare institutions, this typically involves screening of patients, monitoring of those carrying (and/or suffering disease from) resistant pathogens, use of personal protective equipment, and social distancing measures such as isolation and quarantine. In some cases, it also involves decolonization of patients. Methicillin-resistant Staphylococcus aureus (MRSA) decolonization, for example, involves the use of antibacterial solutions on the skin, hair, and nasal membranes. More dramatically, recent studies have reported successful use of faecal transplantation to decolonize those with highly resistant bowel organisms (Freedman and Eppes 2014; Crum-Cianflone et al. 2015). In many cases, screening for resistant pathogens in hospital does not involve/require informed consent of patients, on the grounds that screening and control measures are required in order to prevent harm to others. Such policies should nonetheless be based upon careful ethical justification as well as, where possible, evidence of cost-effectiveness (see Chap. 6), especially insofar as they infringe on the lives of individual carriers (who may or may not be symptomatic) in significant ways (see Chap. 13).
Infection control policies become more complex when they are applied in the general community. As more people in the community are identified as carriers of highly resistant pathogens, it remains to be seen what kinds of restrictions of individual liberty would or shoud be considered justifiable. When, if ever, for example, should travellers be screened on arrival from high-risk regions – and when should those who test positive for resistant organisms be offered (or required to have) decolonization – and/or be subject to monitoring and/or social distancing measures? Important questions such as these need to be considered (and re-evaluated) as more is learned about community and international transmission of drug-resistant organisms.
Vaccines are a cross-cutting intervention with the potential to obviate the need to prescribe antimicrobials for a range of pathogens. In some cases, furthermore, vaccines can prevent infections that would otherwise be untreatable/uncurable (e.g., due to high levels of drug resistance). Existing vaccines against tuberculosis and some bacterial infections (e.g. Streptococcus pneumoniae, Haemophilus influenzae) reduce the incidence of infections due to these pathogens and thereby reduce the use of relevant antimicrobials (Dar et al. 2016). Vaccines against specific resistant strains may also lead to their replacement (e.g. in a given ecological niche in the human body) by strains that are easier to treat (Dar et al. 2016), although longitudinal surveillance data regarding strain epidemiology and disease burden are needed to confirm whether such effects lead to a long-term net public health benefit.
Even effective vaccines against viral infections (e.g. influenza, common cold viruses) can lead to a marked reduction in antibiotic
use since viral infections are often erroneously treated with antibiotics (Neuzil et al. 2000). New vaccines against malaria and typhoid may help to reduce antimicrobial use and resistance relevant to these pathogens. Because there is a great number of resistant pathogens for which we lack vaccines, however, this is an important area in need of further research and development.
Of course, discovering an effective vaccine may lead to the replacement of one collective action problem (antimicrobial overuse) with another (assuring high vaccination rates) – meaning that even this ‘technical fix’ would have limitations. Like the development of new drugs, in any case, new vaccines would form only one part of the multi-pronged approach needed to control the problem of drug resistance.