WHO targets new antibiotics to fight hospital ‘superbugs’

WHO targets new antibiotics to fight hospital ‘superbugs’

New guidance encourages pharmaceutical companies to focus research where need is most urgent, amid a rising AMR threat

The spread of drug-resistant infections continues to outpace the development of new antibiotics Credit: Md Saiful Islam Khan/iStockphoto

Drugmakers must focus on developing new antibiotics to fight hospital “superbugs” including meningitis and other infections that can resist last-line treatments, the World Health Organization (WHO) has said.

The agency on Wednesday released its latest guidance identifying the most urgently needed qualities that future antibiotics should have in order to curb the spread of drug-resistant infections – a rising threat to global health.

Anti-microbial resistance (AMR) – the phenomenon where bacteria develop resistance to the drugs used to kill them – already kills over a million people a year and is forecast to kill 10 million by 2050.

But the spread of drug-resistant infections continues to outpace the development of new antibiotics.

The number of antibacterials currently in development, including both new medicines and experimental treatments like phage therapy, has fallen from 97 to 90 since 2023, as several candidates failed clinical trials. 

Of these, only 15 of these are considered “innovative”, meaning they are entirely new drugs.

The WHO’s guidance, which comes in the form of a technical planning document, is intended to help pharmaceutical companies focus their research where it is needed most urgently.

“We’re in a race against time, and developers at this stage really need concrete milestones to achieve,” Dr Valeria Gigante, the WHO’s global lead for AMR research and development, told The Telegraph.

The document highlights three critical targets for new antibiotics:

• Fighting hard-to-treat Gram-negative bacteria – pathogens with an outer shell that are notoriously difficult to kill.
• Finding new drugs for critically ill patients, particularly those with infections that can no longer be treated with vancomycin, a powerful antibiotic considered a drug of last-resort 
• Developing better treatments for bacterial meningitis, which is often caused by drug-resistant bacteria.

The first priority outlined in the document is the development of new drugs to fight life-threatening infections caused by ‘Gram-negative’ bacteria like Acinetobacter baumannii and Pseudomonas aeruginosa. 

These notoriously difficult to kill pathogens are mostly caught in hospital settings, and tend to affect frail, post-operative patients – leading to serious illnesses like sepsis and pneumonia.

“For Gram-negative infections, the priority is to develop new antibiotics with a ‘novel mechanism of action’ that can treat bacteria resistant to multiple existing drugs,” said Dr Gigante.

Developing these novel antibacterials, which attack bacteria in new ways, is a long and expensive process.

Research and development costs for a single candidate drug can exceed £1 billion and the timeline from discovery to approval can take 10-15 years. It is also extremely difficult – an estimated 95 per cent of candidates will fail.

Market forces also dis-incentivise drug companies from investing in new antibiotics, favouring instead much more lucrative products like cancer and diabetes treatments.

“The WHO always calls for innovation [...] but innovation really takes time,” said Dr Gigante, adding that drug makers should take more risks to ensure doctors have the best tools available.

“There are a lot of financial constraints. We really need to shift our mindset, and now we need a behavioural change to equip clinicians with the right tools and take some risks as part of the innovation process.”

Some progress is being made, however.

For example, a group of scientists in India are testing whether adding certain molecules to existing antibiotics could disable bacterial resistance, making older drugs work again.

A British company, Acrux Pharmaceuticals, is testing a drug called Ibezapolstat, which works by blocking an enzyme called PolC – needed by bacteria to copy their DNA and replicate –  instead of killing the pathogen itself.

It is also hoped that artificial intelligence will help speed up the process of drug discovery by predicting which compounds are most likely to work in curtailing resistance, allowing scientists to focus on the most promising candidates – slashing both time and cost.

The WHO also identified the need for new antibiotics to treat infections in vulnerable patients with weakened immune systems, especially those caused by resistant Enterococcus faecium. 

The bacteria is the leading cause of hospital-acquired infections globally, and is most commonly transmitted to people through invasive medical devices like catheters or pacemakers. 

In Britain alone, more than 4,000 infections are reported every year, according to the UK Health Security Agency (UKHSA). 

It is so dangerous because enterococcus faecium can now resist several families of antibiotics including vancomycin. 

Up to 40 per cent of infections are fatal, causing an estimated 250,000 deaths in North America and Europe every year. 

The third WHO priority is better drugs targeting bacterial meningitis, a severe infection of the brain and spinal cord that kills roughly one in six patients and can cause life-long disabilities, including vision and hearing loss, epilepsy, and brain damage. 

The WHO document focuses on healthcare-associated meningitis – considered the most dangerous form of the disease because it is caused by multidrug-resistant hospital bacteria that spread between vulnerable patients and can survive on medical devices and equipment. 

These infections typically affect patients who have had brain surgery, head injuries, or medical devices like drains or shunts installed.

Damage to the brain’s protective barriers allows bacteria to enter the brain, and 15 to 30 per cent of patients with hospital-acquired meningitis do not survive.

“Bacterial meningitis is getting harder to treat because resistance is rising and many antibiotics don’t reach effective levels in the fluid surrounding the brain, where the bacteria live,” said Dr Gigante. 

Resistance to cephalosporins, a commonly used antibiotic for meningitis, for example, has been reported at up to eight per cent in Asia and 32 per cent in Latin America and the Caribbean. 

New drugs must be able to penetrate this barrier to reach the brain fluid at levels sufficient to kill the bacteria, the WHO says.

The WHO and others have long been sounding the alarm over the state of antibiotics development.

On Tuesday, the Access to Medicine Foundation (AMF), a Netherlands-based non-profit group backed by the Wellcome Trust, warned that the pipeline of new drugs to fight superbugs remains “worryingly thin”.

In a worst-case scenario, failing to address the rising problem of AMR could mean that common issues like urinary tract infections and diarrhoea become untreatable, and life-saving procedures including chemotherapy, c-sections, hip replacements, and organ transplants become incredibly dangerous to perform.

Inadequate research and development will not only contribute to deaths and disability, but by 2050 could result in $1 trillion in global healthcare costs, according to the World Bank.

Dr Gigante said she hoped the WHO’s guidance would lead to innovations that will help tackle AMR, which has sometimes been called the silent pandemic.

“AMR is one of the most urgent public health needs because resistance to available antibiotics is emerging and spreading faster than our ability to develop new and effective medicine,” she said.

“Our antibacterial pipeline remains too limited and lacks innovation [...] The ultimate goal is that future innovation will address these global gaps.”

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