Why is it so difficult to create a new antibiotic?

The discovery of antibiotics is one of the greatest medical breakthroughs of the 20th century. Before antibiotics are given, childbirth, a urinary tract infection, or a simple cut can result in death from infection.

Antibiotics, a type of antimicrobial, have made many modern medical procedures possible and now the global healthcare system relies on them.

With the increasing use of antimicrobials, microbes – such as bacteria, fungi and parasites – have developed the ability to resist the effects of these drugs. The result is that common infections that were once easily treatable are becoming increasingly difficult to cure and, in some cases, fatal.

After the development of penicillin in the mid-1940s, many new classes of antibiotics were developed. However, since the 1980s there has been little investment in the development of new technologies and very few approved.

There is an urgent need for new antibiotics that work against drug-resistant bacteria. Without further action, drug-resistant infections are expected to kill more than 39 million people by 2050.

Why are so few new antibiotics successfully developed for medical use?

Investing in new drugs

Many pharmaceutical companies have left this area of ​​research. Furthermore, it is a huge challenge to find new and different types of antibiotics that are not quickly rendered ineffective by existing antimicrobial resistance (AMR).

Developing a new drug is a complex, extremely expensive and time-consuming undertaking. From initial discovery to approval can take 10 to 15 years and cost more than $1 billion.

Most existing antibiotics are cheap and easily available. Any new antibiotics are generally considered a “last resort” and are only used after all other treatment options have been exhausted. This is intended to prevent the development of resistance to them.

This means that the return on investment for antibiotics is much lower compared to drugs for many other diseases.

It is therefore unlikely that pharmaceutical companies will recoup the costs associated with developing a new antibiotic at the end of a lengthy research process.

Test what works for sure

When searching for new potential antibiotics, researchers screen extracts and compound libraries and also use artificial intelligence (AI) approaches to search for antibiotics that show promising antimicrobial activity.

The scientists then refine and improve the initial results in the laboratory by testing them against infection-causing pathogens. At the same time, they ensure that the compounds are not harmful to humans.

For an antibiotic to work on a patient, it must reach the areas of the body where the pathogen is present in high enough concentrations to eliminate the infection. At the same time, side effects must be minimized.

Scientists need to change many parameters of molecules to ensure safety and effectiveness before moving on to the next stages of development.

After early development, lead compounds must undergo a series of human clinical trials under carefully controlled conditions. This is to ensure that these are, first and foremost, safe and effective in treating the disease.

Current developments

Universities and small companies are now responsible for much of the discovery and early development of antibiotics.

At the Ineos Oxford Institute for Antimicrobial Research we are developing new classes of antibiotics and new combination therapies.

Combination therapy involves giving a patient two or more medications at the same time, with each medication playing a specific role.

A drug is the antibiotic, such as penicillin, and kills the bacteria.

The second drug targets the resistance mechanism that bacteria have developed to evade the antibiotic and acts as an antibiotic sentinel.

By attacking the resistance mechanism, the second drug protects the antibiotic from destruction and allows the antibiotic to clear the infection and cure the patient.

In a possible combination therapy we recently developed, two protective molecules were administered together with an existing antibiotic. This triple combination showed promise against a wide range of drug-resistant bacteria.

However, our work cannot be done in isolation. Supporting and sustaining the antibiotic pipeline requires commitment from governments, the pharmaceutical industry and global health authorities.

One strategy in which the UK is leading the world is to create a subscription model for purchasing antibiotics that is not linked to the number of antibiotics sold.

Health care providers would pay the pharmaceutical company a fixed fee for the antibiotics, based on their benefits rather than the amount used.

This separates demand from profit, making it more economical for companies to develop new antibiotics for global public health.