11.3 Why does antibiotic resistance matter?

11.3.1 What are antibiotics?

Bacteria exist in all environments, including on and within the bodies of animals (i.e. their microbiome). Most cause no harm to health and are even beneficial. However, some are actively harmful (pathogens) and can cause a wide range of diseases (Figure 18).

Figure 18: Some diseases caused by bacterial infections.

Antibiotics are the group of medicines and chemicals used to treat these pathogenic bacteria and the diseases that they cause. They form a sub-group of a wider class of substances known as antimicrobials that are used to target a wide range of pathogenic microbes such as parasites, fungi, and viruses, in addition to bacteria.

Before antibiotics, many infectious diseases were untreatable and some frequently resulted in death – a situation that still exists for many people living in poverty in low-income countries. The power to reliably treat infection is a foundation of modern medicine, critical for reducing the risks for patients facing major surgeries and those with compromised immune systems (Figure 19).

Figure 19: Diseases caused by bacterial infections. Reproduced from Jørgensen. et al. 2017.

All antibiotics help the body’s natural immune system to fight bacterial infections but do so in different ways. Today, there are well over 100 antibiotic drugs available that fall within a very limited number of ‘classes’, which are grouped according to the similar ways in which they target bacteria (Figure 20).

Figure 20: An overview of the different classes of antibiotics. Reproduced from Compound Interest. 2014.

Some ‘broad spectrum’ antibiotics are effective at killing a wide range of different bacteria, whereas ‘narrow spectrum’ antibiotics target only specific types of bacteria. Side-effects from antibiotics also range hugely, and in some cases, can themselves cause very severe health impacts – often making them drugs of last resort, used only when everything else fails.

11.3.2 How do bacteria develop resistance to antibiotics?

‘Antibiotic resistance’ refers to a situation where a specific type of antibiotic drug is not effective at treating an infection caused by a specific bacterial species or strain.

Bacteria species: the huge genetic diversity of bacteria, make the species concept much less precise than for larger organisms. Broadly, it denotes a generic group of bacteria which all share a certain amount of genetic similarity (akin to that between humans and all primates) and so have similar functional characteristics.

Bacterial strain: in contrast to a species, a strain denotes a specific population of bacteria that share a very close genetic similarity. Strains are subtypes of a bacterial species existing in a specific context, which can have unique characteristics that differ from other bacteria of the same species.

This may happen for two reasons:

  • Intrinsic resistance: antibiotic resistance is a natural outcome of the bacteria’s unique biology. In nature, antibiotic compounds are produced by many microorganisms to kill one another and discovering these compounds has formed the basis for most current antibiotic drugs. As a result, resistance to antibiotics has evolved and is found widely in natural settings, with some bacterial species having an intrinsic resistance to some types of antibiotic compounds.
  • Acquired resistance: a specific population of bacterial cells that previously were sensitive to an antibiotic compound, may evolve by acquiring new genetic solutions and so biological capabilities, that enable it to disable the drug’s ability to do them harm.

For public health, acquired resistance is of major concern because it can progressively erode the efficacy of existing antibiotic drugs. The introduction of new genetic traits conferring resistance to a drug, may occur in two distinct ways:

  1. Random mutation: bacterial strains are composed of huge numbers of cells that replicate very quickly. Random mutations can result in genetic variation between bacterial cells in a strain, some of which may confer resistance to a drug.
  2. Horizontal gene transfer: different strains and species of bacteria that come into contact with one another are able to exchange genetic traits between them, including those conferring resistance to one or more types of antibiotic drug.

Once some bacterial cells have acquired resistance, these will have a greater likelihood of surviving when exposed to the drug, while other cells will selectively be killed-off. Most remaining cells will thus have resistance genes, multiply rapidly, and so become predominant in the overall population (Figure 21).

Figure 21: How antibiotic resistance occurs via a process of selection pressure. Reproduced from MSU. 2017.

Because of this, the use of antibiotic drugs will always create the driving conditions for resistance to emerge (known as selection pressure), and evidence shows that this can happen quickly (Figure 22). Once resistance has emerged, it can persist long after the use of antibiotics has stopped, and in some contexts, may never fully disappear.

Figure 22: Resistance has evolved to all major classes of antibiotics on the market. Reproduced from Jørgensen. et al. 2017.

Pathogens other than bacteria (e.g. parasites, fungi, and viruses) can also evolve in response to antimicrobial drugs, and so the problem of resistance is, in fact, a much broader issue that goes beyond just antibiotics and bacteria. 

11.3.3 Why is stewardship of antibiotic drugs needed?

Antibiotics (like vaccinations) are unusual medical tools because each instance of their use has social and ethical implications that reach far beyond the individual human or animal that they are being used to treat. 

While individuals may benefit from using an antibiotic drug today, the contribution this makes towards the emergence of resistance in the local or global community can deny that same opportunity for effective treatment of disease to others, and to future generations.

Effective antibiotic drugs currently in existence, must, therefore, be seen as being finite, non-renewable resources – or as an eroding foundation upon which, modern medicine is dependent. The degree to which new technologies and methods are able to deliver effective and cheap substitutes for currently effective drugs is widely debated, and highly uncertain.

If the supply of newly developed drugs were always able to substitute, perfectly, for older antibiotics that have begun to fail, there would not be a problem. But currently, this is not the case (Figure 23):

  • Rates of observed antibiotic resistance are increasing – often to multiple drugs at once;
  • The rate of new drug discovery and number of companies working on it has substantially declined in recent decades;
  • Access to new drugs is also inequitable, as high costs of development make them unaffordable for those with low-income;
  • Drugs of last resort – often with severe side-effects – are increasingly being used. And even to these, resistance is emerging.
Figure 23: Relationship between antibiotic resistance, research and approval of new antibiotics between 1980 and 2010. Reproduced from Cooper and Shales. 2011.

Data and statistics on the total impact of antibiotic-resistant infections worldwide are not comprehensive or reliable but are thought to be large. In places where health data exists like the European Union, estimates indicate substantial impacts: 25,000 deaths from antibiotic drug-resistant infections and EUR 1.5 billion in economic costs.

For antibiotic infections to remain treatable, the rate at which resistance develops and spreads must be slowed, and new drugs also need to be developed. However, conserving antibiotic resources presents huge challenges.

Antibiotics are easily available for human and animal use in almost all countries worldwide, with very few, if any, restrictions on their use in many regions. While this may benefit a particular individual at any one time, the collective contribution this makes towards increasing antibiotic resistance is ultimately harmful to everyone.

Out of this situation has come the concept of antibiotic stewardship that is now widely supported, summarised by Prescott (2014) as follows:

“The concept is evolving but basically describes the multifaceted approach required to optimize the use of antibiotics while minimizing the development of resistance and of other adverse effects. The term stewardship resonates with the acceptance of responsibility for the long-term management of something of enormous value”.

Priorities for antibiotic stewardship include:

  • Avoidance of any unnecessary uses of antibiotics and so the development of resistance;
  • Selection of the most effective drug(s), doses, and treatment duration for a given situation;
  • Ensuring that recommended treatments are carried out accurately and fully;
  • Containing and mitigating the spread of any antibiotic resistance that does arise.

11.3.4 How is antibiotic resistance a form of environmental pollution?

Antibiotic resistance may arise in humans or animals following treatment and may be driven to evolve in bacteria living in the wider environment by the release of antibiotic drugs that are left-over in human or animal effluent, or via the environmental release of antibiotic drugs from industrial processes.

Once this has taken place, there are many pathways – direct and indirect – by which antibiotic resistance can be transmitted, with its spread potentially accelerated by modern transport networks, wildlife movements, agricultural practices, and flows of water (Section 11.1.2; Figure 24).

It follows that the emergence of antibiotic resistance in one place, can at lease potentially, lead to antibiotic resistant bacteria or the genes carrying resistance being spread to anywhere else.

Figure 24: Diagrammatic representation of movement of resistance genes in bacteria through different routes. Reproduced from Prescott. 2014.

Bacteria’s ability to share resistance genes between one another, has particularly important implications. In hospitals, for example, because multiple patients, diseases, and drugs coexist within a confined area, the sharing of resistance genes between different strains of pathogenic bacteria can result in ‘superbugs’ that are multi-drug resistant and so untreatable.

Pathogenic bacteria may also acquire resistance through their encounters with more benign bacteria commonly found living in or on human or animal bodies, or from bacteria encountered in the wider environment (Figure 25).

Figure 25: Schematic representation of the interactions between pollution, resistant bacteria and aquatic environments. Reproduced from Hernandes Coutinho, et al. 2013.

Antibiotic resistance in environmental bacteria is driven by the release of antibiotic resistant bacteria and large volumes of antibiotics (at low doses) into the natural environment, via human and animal waste streams.

As the overall reservoir of resistance genes in the natural environment accumulates – a concept known as the environmental resistome – so too does the overall risk of antibiotic resistance being transferred to human pathogenic bacteria.