How do we solve antibiotic resistance?

Fred Schwaller

DW
01/13/2023

Antibiotic resistance threatens to take us back to a time before penicillin when the majority of deaths were caused by infections. What are we doing to solve the crisis?

Since antibiotics were introduced to the world in the mid-20th century, deaths attributable to infections dropped from over 50% to 10-15%. Experts have been warning for decades that the threat of antibiotic resistance could take us back in time to when even simple infections were deadly.

But how serious is the issue really?

A study in 2019 found more than 1 million peoplea year died from infections linked to microbes that are resistant to antibiotics — more than those who died due to malaria or with HIV/AIDS.

Experts describe antibiotic resistance as one of the greatest challenges facing humanity. They predict that if the problem remains unsolved, 10 million people could die as a result by 2050.

"Antibiotic resistance will remain a problem for the foreseeable future," said Paul Blainey, a biological engineer at the Massachusetts Institute of Technology. "Maintaining modern medicine and standards of health in the way we know them today will depend on the development of new antibiotic drugs."

Illustration of Legionella pneumophila bacteria, the cause of Legionnaires disease. Pneumophila bacteria have high levels of resistance to antibiotics.

Science Photo Library/IMAGO

What causes antibiotic resistance?

Antibiotic resistance occurs when bacteria evolve to evade antibiotics. Overuse and misuse of antibiotics are the biggest drivers of resistance. That means that the more we use antibiotics, the worse the problem of antibiotic resistance becomes.

Antibiotics work by binding to a specific target protein on a bacteria, then entering to kill it from the inside. Penicillin, for example, weakens the bacterial cell wall, causing the cell to disintegrate.

The most common ways bacteria evade antibiotics come from mutations that allow them to stop drugs from binding to bacteria. It's like the bacteria changed the locks so the antibiotic key no longer opens the cell door.

"Bacteria can also achieve resistance by producing proteins that inactivate or modify the antibiotic, so it no longer binds to the bacteria. Or the target protein is mutated so the antibiotic can no longer bind to it," said Gerry Wright, a biochemist who specializes in antibiotic resistance.

But worst of all is when bacteria evolve many of these mechanisms in backup, so even if you overcome one, other resistances might fill the gap.
Solving the problem of antibiotic resistance

Antibiotic resistance will always be with us. It's the nature of evolution by natural selection that means bacteria will always find ways to evade antibiotics.

But experts are optimistic we can find ways to limit antibiotic resistance in the next decades, at least enough to stop the issue from spiraling into a bigger crisis.

"I'm hopeful we can overcome the concerns about antibiotic resistance. Scientists in the field are dedicated to solving these big problems and preserving our ability to control infectious diseases that is so important to our quality of life," said Wright.

Unfortunately, it isn't as simple as developing a drug that will permanently overcome antibiotic resistance. It's incredibly complex science, even more so than finding a vaccine for a virus such as COVID-19. For one, there's huge diversity among bacteria — not all drugs work on a given organism, and not all organisms are killed by a given drug.

Option 1: Modify existing antibiotics

Scientists have been working on the issue from many different angles. One approach is to modify old antibiotics so they overcome resistance.

"Penicillin and cephalosporin antibiotics have undergone many rounds of modifications by medicinal chemists to improve their drug-like properties and overcome resistance," said Wright.

But Wright explained that the ability to tinker with these structures is not infinite. It's more of a delaying tactic than fundamentally fixing the core issue of antibiotic resistance.

"At some point, there are diminishing returns in that new compounds either have poor drug-like properties or toxicities that make them unsuitable," he said.

Toxicity is the ability of a substance to have a poisonous effect and either cause harm or death.

Option 2: Develop new antibiotics

Another strategy is to make brand-new drugs, but this approach hasn't been very successful in recent decades.

"The reality is that the last genuinely new chemical structure that has resulted in a drug that is currently being used in humans was discovered in the mid-1980s," Wright said.

But there are some signs of progress. For one, scientists are now armed with much more sophisticated drug discovery technologies, not least artificial intelligence (AI).

"Examples of scientific innovations include computational machine learning approaches to screen drugs in silico, and methods to screen many different combinations of compounds for antibiotic effects," said Blainey.

"In silico" refers to experiments performed via computer simulation.

These new innovations are helping scientists overcome older challenges in drug discovery. The hope is that antibiotic-resistant drugs can be pushed through drug development pipelines quickly enough for them to make an impact in global health care.

But central to the issue is that antibiotic resistance develops quickly whereas antimicrobials — the basis of antibiotic drugs — are developed slowly. Scientists hear the clock ever ticking.

Borrelia burgdorferi bacteria shown here are responsible for causing Lyme disease. These bacteria are yet to develop resistance to antibiotics.

Callista Images/imago images

Global fight against antibiotic resistance lacking

As with the race for COVID-19 vaccines, overcoming antibiotic resistance will require tremendous international effort dedicated to the problem. But that's exactly what's missing.

"What makes the resistance challenge so acute in 2023 is that there is no longer a well-organized, well-funded, and functioning pipeline of new drug candidates, yet resistance continues to emerge," said Wright.

Reports indicate there were 43 antibiotics in clinical trials or pending approval in December 2020. For comparison, over 1,300 anticancer agents were at similar stages of development.

Blainey said that many of the issues here came from the commercialization of drug development.

"Sadly, some large companies have given up their antibiotics programs based around commercial considerations and several small companies developing new antibiotics have failed financially before their candidates reached the clinic. We really need more investment in all antibiotic discovery strategies," he told DW.

Buying time with antibiotic regulation

In the short term, some experts want more regulation of antibiotics so their use is limited to situations when they are strictly necessary. The hope is this will buy us some time to slow down antibiotic resistance while drug discovery catches up.

Antibiotics are not well regulated in many parts of the world. For example, antibiotics were "flying off the shelves" during the COVID-19 pandemic in India, where people can buy them over the counter in pharmacies.

Limiting the use of antibiotics in agriculture would also have a major impact, experts say.

The EU and US have banned the use of antibiotics for livestock growth, and in 2022, the EU brought in legislation to prohibit all forms of routine antibiotic use in farming.

Edited by: Zulfikar Abbany