Antibiotic resistance is a major global health burden, responsible for millions of infections and hundreds of thousands of deaths each year. A landmark 2014 report by the World Health Organisation (WHO) highlighted that antimicrobial misuse was driving antibiotic resistance worldwide. Since that report, some progress has been made, but new challenges have also emerged, which we will address in this article.

Antibiotic resistance: a growing global threat

Antibiotic resistance refers to the ability of bacteria to survive and grow despite treatment with antimicrobial drugs. Nowadays, more and more bacteria carry collections of antibiotic resistance genes within their microbiota, which is known as the "antibiotic resistome" concept.

The mid-20th century was the "golden era" of antibiotic discovery. Unfortunately, this resulted in antibiotic misuse, such as taking antibiotics when not called for (e.g. treating a viral infection) or failing to complete the full treatment course, which was not seen as serious at the time and led to antibiotic resistance.

The major causes now remain misuse, compounded by a lack of new drugs. The development of new antibiotics is not financially profitable, and due to strict regulatory requirements, pharmaceutical companies have decreased research and production of new antibacterial agents.

In addition, the reasons continue to grow. Some causes include overpopulation, poor sanitation, inadequate sewage disposal systems in some countries, selective pressures, and excessive use of antibiotics in clinics and livestock.

Alexander Fleming, the discoverer of penicillin, warned in 1945: "The public will demand the drug, and then will begin an era … of abuses." Sadly, this prediction came true, mostly because of the use of antibiotics in animals. In 2010, global antibiotic use in livestock was estimated at over 63,000 tons. Since then, new legislation in some countries has limited the use of antibiotics for growth promotion in animals, but the practice remains common in many parts of the world.

Antibiotic resistance in the post-COVID era: 3 rising challenges

Biofilms

Biofilms are a clever defence mechanism used by many bacteria to help them resist antibiotics. They work by creating a slimy protective membrane that prevents antibiotics from penetrating the bacteria, allowing them to survive and multiply even in harsh conditions for long periods of time. Biofilms form around bacterial colonies and provide a safe environment for bacteria to thrive.

Some pathogens that form biofilms are particularly difficult to treat with antibiotics. One example is Pseudomonas aeruginosa, a bacterium responsible for many catheter-associated urinary tract infections (CAUTIs) in hospitals. In recent years, the rate of P. aeruginosa-related CAUTIs has increased. The main method of infection is through catheters, where bacteria can attach and quickly form biofilms, making infections harder to eliminate. P. aeruginosa enters the urinary tract, forms a biofilm, and this often leads to standard antibiotic treatments failing, requiring stronger or combination therapies.

Antibiotic overuse and disinfectant exposure during COVID-19

During the COVID-19 pandemic, antibiotics were frequently prescribed even in cases where bacterial infections were not confirmed, due to uncertainty in diagnosis. Social distancing and restrictions meant that many patients relied on online consultations. Many COVID-19 symptoms, such as fever, cough, and fatigue, can resemble bacterial infections, making it difficult to determine the cause without thorough testing. As a result, antibiotics were sometimes given as a protective measure, leading to overprescription and giving bacterial populations more opportunities to develop resistance.

In addition, the continuous use of hand sanitisers and disinfectants may have played a role in antibiotic resistance. Microbial populations can gradually adapt to chemical agents when exposed to different amounts and formulations, as occurs with various disinfectants and cleaning sprays. Over time, this exposure may lead to the development of resistance genes as bacteria evolve new mechanisms to survive chemicals that would normally kill them. The result is the creation of small, resistant bacterial populations, which may increase tolerance to antibiotics, especially in biofilm-related infections, making them even harder to treat. This remains a hypothesis under study but is considered a potential effect of the COVID-19 pandemic on antibiotic resistance.

Superbugs and multi-drug resistance

Superbugs are bacteria that have developed resistance to many types of antibiotics, making them very difficult to treat. Infections caused by superbugs lead to higher rates of illness and death, longer hospital stays, and the need for stronger and more expensive treatments. They have developed mainly due to the overuse of antibiotics in hospitals and increased exposure in both healthcare and community settings.

Some common superbugs that play a major role in prolonged hospital stays include E. coli, Proteus species, Pseudomonas aeruginosa, Salmonella species, and Staphylococcus aureus (S. aureus). E. coli is well known for causing urinary tract and bloodstream infections. Today, some strains of E. coli are resistant to multiple antibiotics, making treatment much harder. Proteus species often cause urinary tract or wound infections in hospitalised patients. For example, Proteus mirabilis can lead to complicated catheter-associated infections. Pseudomonas aeruginosa is frequently found in hospital environments and is known for forming biofilms, which protect it from antibiotics. Salmonella species cause foodborne illnesses and are often contracted from raw or undercooked poultry and eggs. Certain strains are resistant to multiple antibiotics. Finally, Staphylococcus aureus, particularly Methicillin-resistant S. aureus (MRSA), is considered one of the most dangerous superbugs of the 21st century. MRSA can cause skin infections, pneumonia, and life-threatening bloodstream infections, and it is resistant to many commonly used antibiotics. The rise of these superbugs highlights the urgent need for better antibiotic stewardship, as well as better antibiotics and alternative treatments.

Next-generation tools to beat antibiotic resistance

Nanoparticles and gene editing to combat biofilm formation

A new strategy currently being heavily researched to combat biofilm formation is the use of nanoparticles. Nanoparticles act like tiny delivery drones that help bypass the biofilm, the "slime fortress" that bacteria use to protect their colonies. In addition, nanoparticles can be combined with gene-editing systems. These systems work by finding specific DNA sequences in bacteria and cutting them, effectively turning off genes that allow bacteria to survive, resist antibiotics, or form biofilms. When combined with nanoparticles, gene-editing systems like CRISPR/Cas9 can be delivered efficiently into the biofilm, targeting and destroying bacteria from within.

Traditional treatments often get trapped in the biofilm and miss their target, but nanoparticles provide a way to bypass these defences. According to research, gold nanoparticle carriers with CRISPR/Cas9 formulations have been shown to reduce Pseudomonas aeruginosa biofilm biomass by over 90% in vitro, suggesting they are a promising avenue for future treatments.

AI and machine learning for antibiotic discovery

The development of artificial intelligence (AI) and machine learning (ML) has the potential to revolutionise antibiotic discovery. AI focuses on developing systems based on human-like intelligence, capable of recognising patterns, understanding data, and reaching conclusions. ML uses algorithms to process and improve predictions from large datasets.

Together, AI and ML can analyse vast amounts of data, helping with drug design, drug repurposing, and synergistic therapies by screening extensive libraries of chemical compounds against antimicrobial-resistant (AMR) pathogens. While there is still progress to be made before these systems are perfect, AI/ML techniques already include supervised learning algorithms, unsupervised learning algorithms, reinforcement learning (RL), and deep learning (DL) architectures. Supervised learning algorithms can use labelled datasets, such as patient records or microbial genomic data, to make predictions and guide decisions. For example, supervised machine learning has identified genetic traits associated with antibiotic sensitivity in Escherichia coli across various sequence types, helping scientists understand how sequence types evolve and spread within populations. By using AI and ML, researchers can speed up the discovery of new antibiotics and improve strategies to combat resistant bacteria.

FAQs

What can I do on a personal level to help combat antibiotic resistance?

Some good habits to adopt include:

• Antibiotics: Only use antibiotics when prescribed by a doctor and complete the full course
• Vaccinations: Stay up to date with vaccines to prevent infections and help reduce the need for antibiotics
• Food choices: Choose products labelled antibiotic-free when possible to support the responsible use of antibiotics in agriculture

Who is most at risk from antibiotic resistance?

The main people at risk are:

• Hospitalised patients: Especially those with long hospital stays, catheters, or ventilators
• Immunocompromised individuals: Such as the elderly, infants, or patients undergoing chemotherapy
• Individuals with frequent antibiotic exposure: Such as those with chronic infections or who require frequent medical treatments

What was the golden age of antibiotics and why don't we make more now?

The Golden Age of Antibiotics was a period from the 1940s to the 1960s, when many life-saving antibiotics, such as penicillin, streptomycin, and tetracyclines, were discovered. During this time, infections that were once deadly became treatable for the first time. Today, fewer new antibiotics are being developed because research and development is expensive and often not profitable for pharmaceutical companies. In addition, strict regulations and lengthy approval processes make bringing new antibiotics to market slow and costly. Finally, bacteria rapidly develop resistance, which can shorten the effective lifespan of a new drug, reducing financial incentives.

Summary

Antibiotic resistance is a bacterium's ability to withstand drugs that could once kill it. It has become a serious problem in the 21st century because bacteria are developing resistance to more and more treatments, creating superbugs and multi-drug-resistant strains. The main causes include the slow discovery of new antibiotics, reduced research into their development, and the misuse and overprescription of existing antibiotics. New challenges following COVID-19 may include the influence of hand sanitisers and increased use of disinfectants, which some studies suggest may promote resistance as bacteria adapt to survive repeated chemical exposure. Another major challenge is biofilms, which are protective layers that make bacteria harder to eliminate. Promising new strategies expected to be implemented include the use of nanoparticles and gene-editing systems, as well as AI and ML.