What Is Antibiotic Resistance?

Overview

Antimicrobials are a group of drugs used to treat infections caused by microorganisms, such as bacteria, viruses, fungi or parasites. Antibiotics are a subset of these drugs that specifically target bacterial infections. Despite being crucial to treating and managing serious infections, over-reliance on antibiotics has created a global antibiotic resistance crisis. In this article, we will explain what antibiotic resistance is, how it develops, and what doctors and patients can do to help prevent it.

The basics of antibiotics

Since penicillin was first mass-produced in 1942, antibiotics have been fundamental in treating infections.¹ Some estimates suggest that by allowing doctors to treat and cure previously deadly diseases, antibiotics have extended the average life span by two decades.² 

Antibiotics treat infections by killing the bacteria causing the illness or preventing it from spreading. Antibiotics may be given as tablets, topical creams or injections. As antibiotics specifically target bacteria, they are not effective for treating other microorganisms such as viruses (e.g., flu). 

How do antibiotics work?

Antibiotics work by either eliminating bacterial cells by stopping them from reproducing or disrupting vital chemical processes that keep them alive. Antibiotics are generally categorised into two groups: bactericidal and bacteriostatic. Bactericidal antibiotics actively kill bacteria, while bacteriostatic antibiotics prevent growth.

How well antibiotics work depends on various factors, including:⁵

• How the body processes them
• The type of microbe involved
• How much of the microbe is present
• Where the infection is located

Types of antibiotics

Antibiotics are either ‘broad-spectrum’ or ‘narrow-spectrum’. Certain antibiotics only work against certain microbes. For example, vancomycin can penetrate the cells of some bacteria, but not those with a different type of cell wall.⁵ Broad-spectrum antibiotics are normally effective against many species, whilst narrow-spectrum antibiotics tend to only work on one or a few species.⁶

There are six main groups of antibiotics, listed in the table below alongside some examples and conditions they are often prescribed for.

Antibiotic treatment

When a patient first seeks medical help the cause of the infection is not always clear. Doctors often start antibiotic treatment before a specific diagnosis is confirmed. This type of treatment is called empiric therapy and aims to cover a wide range of potential causes.

Prophylactic therapy is used to prevent infections in patients who aren't currently sick. For example, people with weakened immune systems might get preventive antibiotics against specific infections. Before surgeries or in certain injuries like animal bites, doctors might also give prophylactic antibiotics to prevent infections.

The seriousness of a potential bacterial infection determines how aggressively antibiotics are used. In life-threatening situations like sepsis, doctors quickly administer broad-spectrum antibiotics to cover a wide range of possible bacteria. Once test results are available, the treatment can be adjusted based on the specific infection.

Different factors about the patient are considered when prescribing antibiotics, such as:

• Age
• Allergies
• Kidney and liver function
• Medical history
• Immune system health
• Recent antibiotic use

These factors affect how the body processes and responds to antibiotics, influencing the dosage to ensure the best results.^5,6

What is antibiotic resistance?

The frequent use of antibiotics in medicine and industries like farming has caused microbes to develop ways to resist antibiotics to survive.

Doctors use a measure called the ‘minimum inhibitory concentration’ or MIC to see how resistant microbes are to specific antibiotics. This measures the lowest concentration of an antibiotic required to prevent the microbe from growing in the lab. If the MIC is high, it means the microbe is resistant to that antibiotic.

Microbes have a few methods of resisting antibiotics. They can actively pump out antibiotics from their cells, or prevent the antibiotic from entering in the first place. They can also attack the antibiotic with chemicals to break it down or change its structure to make it ineffective. Bacteria can avoid antibiotics by mutating, changing or shielding the specific site that the antibiotic gains access to the cell, or losing the site altogether.^5,7

How does antibiotic resistance develop?

Every time a new antibiotic is developed, resistance follows, sometimes soon after. Only a decade after the first clinical trials of penicillin, resistance to the drug in Staphylococcus aureus - a common cause of skin and wound infection - was found in 50% of cases.²

Microbes can be naturally resistant if they don't have the target of antibiotic attacks. Some can also gain ‘acquired resistance’ by mutating or, in bacteria, getting genes from other bacteria. A single microbe can have more than one type of resistance.⁵

When antibiotics are used, ‘selective pressure’ is put on microbes. This means microbes that are more resistant to the antibiotic are more likely to survive and pass on their genes, and more bacteria become resistant. Microbes reproduce very quickly, multiplying by the billions, meaning there are many opportunities for mutations to occur that might give microbes resistance to antibiotics.^2,8 

Overuse of antibiotics has caused them to become less effective and has led to the emergence of bacteria that are resistant to multiple antibiotics. These are called ‘multi-drug resistant organisms’, but are also more commonly known as “superbugs”. Some examples of these include Methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, drug-resistant tuberculosis and resistant strains of the yeast, Candida auris.⁹

Consequences of antibiotic resistance

Impact on individual health

If antibiotics are used excessively or an infection is antibiotic-resistant, this can put the patient’s health at risk. Antibiotic-resistant infections are known to increase the length of illness, the risk of complications, survival chances and the odds of repeat infection.

A common example of antibiotic-resistant infection is C. difficile infection, which causes nearly half a million infections per year in the US alone. Almost 17% of C. diff infections will reoccur within 2 months, and in patients over 65, the fatality rate within a month of infection is 9%.¹⁰

As well as causing more serious infections, the increased concentrations and reduced options for antibiotics may lead to more severe side effects. These side effects can include nausea and diarrhoea.

Global public health threat

The World Health Organisation (WHO) recognises antibiotic resistance as one of the main threats to public health. In 2019, deaths caused directly by bacterial antimicrobial resistance were estimated to be 1.27 million.¹¹

Antibiotic resistance affects countries worldwide, with poverty increasing its drivers and consequences by limiting access to appropriate antibiotic treatments and the ability to manage resistant infections. This jeopardises the gains made by modern medicine, making infections more difficult to treat and making routine medical procedures riskier.¹²

One of the main examples of this is multidrug-resistant tuberculosis. It has been found in 84 countries, and nearly 4% of new cases and 20% of treated cases worldwide are caused by strains resistant to antibiotics that were previously effective. Currently, only 50% of multidrug-resistant tuberculosis can be successfully treated with available antibiotics.^12,13

Increased healthcare costs

Antibiotic resistance is exceptionally expensive to manage. Estimates by the WHO predict that by 2050 the healthcare costs caused directly and indirectly by antibiotic resistance will be around US$ 1 trillion.¹²

Causes of antibiotic resistance

Overuse and misuse of antibiotics

In the US, about half of the prescribed antibiotics were found to be incorrect, and nearly one-third were unnecessary for patients in hospitals. Incorrect antibiotic use has become a public health concern.¹⁴ As well as the impact on individual health, inappropriate use of antibiotics has been shown to increase resistance, cases of severe disease, and the reliance on antibiotics to treat minor infections that can normally be recovered without treatment.^13,15

Global travel 

The increase in global travel means resistant strains can spread quickly across borders. This is worsened by the fact that in some countries, antibiotics are sold without prescriptions and widely misused.^2,15

Agricultural practices and antibiotic use

Antibiotic misuse is not just an issue in healthcare. Livestock are often given antibiotics as a precautionary measure to avoid illness, rather than maintaining good hygiene. Around 80% of antibiotics produced in the US are used in the agricultural sector.² This creates a breeding ground for resistant strains that can pass to humans through the environment or the food we eat.¹⁵

Lack of new antibiotic development

The industrial production of antibiotics was a breakthrough for the pharmaceutical industry, but the number of major pharmaceutical companies investing in discovering and developing new antibiotics has decreased. Since 2017, only 12 antibiotics have been approved as of 2023, with the majority being modified versions of existing antibiotics for which there are already resistant strains.^2,12,15,16

How to prevent antibiotic resistance

The key priorities for antibiotic resistance outlined by the WHO include:¹²

• Preventing infections
• Ensuring access to effective diagnosis and treatment
• Gaining vital information on resistance through monitoring and research

Responsible antibiotic use

The most important way patients can help stop the spread of antibiotic resistance is by using them responsibly. This means following the instructions provided by the doctor or prescription sheet. If a dose is missed, take one as soon as you remember or wait until the next dose if it is soon. You should never take a double dose to make up for missing one.

Never share antibiotics or save them for later use - your pharmacist can give you advice on how to dispose of them safely. If you take antibiotics you haven’t been prescribed, you may become more ill or suffer side effects.

Most mild infections can heal without antibiotics, and you are unlikely to be prescribed them for ear, chest or throat infections. This is particularly true when suffering a chest infection, as many of these are caused by viruses that cannot be treated by antibiotics.

Antibiotics may be provided if the infection doesn’t clear, if you are at risk of infecting others, or if there is a chance the infection may become more serious. Patients who are at high risk of infection, such as those with poor immune health, may be given antibiotics as a preventative measure.

Advocating for antibiotic stewardship

Antimicrobial stewardship is the principle of improving the effectiveness and safety of antibiotic use, as well as reducing healthcare costs. Many healthcare organisations have stewardship programmes to help combat issues with antibiotic misuse. These programmes' main focus is educating patients on how to safely use antibiotics.^5,14

Innovations and research in antibiotics

New approaches to antibiotic treatment

As antibiotic resistance has spread, the way antibiotics are used has changed. Doctors face a difficult decision on whether antibiotics are required for each infection. Research has shown delaying antibiotic prescription for minor infections can help reduce how heavily patients rely on antibiotics, without causing further illness.¹⁴

Better methods of quickly diagnosing the microbe causing an infection, and what it is already resistant to, can give them more certainty on whether to use antibiotics and which ones will work.¹³

New treatments for infection

Research has increasingly focused on alternatives to antibiotics. Many plants and animals have evolved to produce proteins that can function like antibiotics, and discovering these is a major field of research. It may be the case that using other microbes could help address the antibiotic-resistant crisis. For example, viruses known as bacteriophages can target and kill specific bacteria. Beneficial bacteria introduced to the body as probiotics can also help reduce infections with harmful bacteria such as C. difficile.¹⁴

One health: a global collaboration in research

It is crucial to recognise that antibiotic resistance is not just caused by the actions of people providing or receiving healthcare, but also those responsible for animal and environmental health. By acknowledging this, individuals and organisations can cooperate to prevent antibiotic resistance. This common aim to improve human, animal and environmental health is called the ‘One Health’ approach.¹⁵

Summary 

Antibiotic resistance is one of the most important healthcare issues today and impacts everyone. However, by educating ourselves and others on how antibiotic resistance appears and spreads, it is possible to continue to safely use antibiotics and help combat antibiotic resistance as new research promises to reduce our over-reliance on them.