How a medieval ‘leechbook’ could be the latest cutting-edge treatment to beat superbugs

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Could novel vaccines or even a medieval recipe for eye balm provide new ways to defeat the teeming armies of antibiotic-resistant superbugs?

There is no doubt we desperately need new solutions to tackle infectious bacteria: the World Health Organisation (WHO) lists antimicrobial resistance as a top ten global health threat, saying that by 2050 it will kill more people than cancer if resistance keeps rising at current rates.

Nor can we rely on better antibiotics.

In April, the WHO warned that none of the 43 antibiotics now being developed can beat the world’s 13 most lethal bacteria, such as Acinetobacter baumannii and Pseudomonas aeruginosa, both of which cause blood infections and pneumonia.

So scientists are taking a different tack and developing powerful non-antibiotic alternatives.

Vaccines are one of the most promising candidates.

Of course, we normally think that vaccines protect us against viruses such as Covid, but investigators are learning how to wield them against killer drug-resistant bacteria, either to treat infections or to prevent them.

Last month, U.S. researchers announced they have developed a vaccine against antibiotic-resistant Klebsiella pneumoniae, which causes pneumonia and infects some 10,000 people in England and Wales each year.

To alert our immune systems to recognise and attack the Klebsiella bacterium, the scientists took a tell-tale protein from its outer skin and inserted it onto the outside of an inactive form of E. coli bacteria.

In tests, inoculated mice successfully beat off Klebsiella infection, researchers at Tulane University reported in the journal Science Immunology.

What’s more, rather than being injected, the vaccine only needs to be inhaled, making it easier to protect vulnerable patients in hospitals.

Inhaling the vaccine also appears to prime the lung’s immune cells very efficiently to fight infection from bacteria, the researchers found.

Dr Jay Kolls, a professor of internal medicine who led the study, says this approach could defeat other multi-drug-resistant species of lung-infecting bacteria.

‘The major cause of pneumonia in the world is Streptococcus pneumoniae, and there’s no reason why this technology theoretically couldn’t be used for that pathogen as well,’ he says.

Vaccines are also being developed against common bacterial illnesses that are often resistant to antibiotics.

In another study published last month, Canadian researchers reported how one vaccine has showed up to 90 per cent success in protecting women against the misery of recurrent urinary tract infections (UTIs) in a trial involving more than 1,400 patients.

The vaccine, called Uromune, is delivered by an oral spray and contains inactivated bacteria of the four most common resistant strains that cause UTIs. This primes patients’ immune systems to target them.

It has already been given to more than 20,000 women in Canada as part of a pre-approval safety-testing programme.

But while the National Institute for Health and Care Excellence says antibiotic-resistant UTIs are increasing, the Uromune vaccine is not yet approved for NHS use (although the treatment may be obtained privately). Regulators are waiting for the outcome of long-term international trials.

Meanwhile, scientists in Spain revealed this month that they have developed a novel way of killing lethal antibiotic-resistant bacteria — by pitting infectious bacteria against each other.

The new approach by scientists at the Centre for Genomic Regulation and Pulmobiotics in Barcelona came out of research into antibiotic-resistant Staphylococcus aureus that grows on the surfaces of implants such as catheters, pacemakers and artificial hips, causing deeply invasive and highly dangerous infections.

Staph A is responsible for 80 per cent of all infections acquired in hospital settings, and these infections are highly resistant to antibiotics, often with far-reaching and devastating consequences.

A 2019 UK study in the journal EFORT Open Reviews, led by Imperial College London, revealed that more than 1,000 potentially risky operations have to be performed in the UK each year to replace infected artificial knee joints alone, at an estimated cost of £100,000 per patient.

‘Prosthetic joint infection is one of the most feared complications of knee-replacement surgery due to its resistance to therapy with existing antibiotics,’ said the researchers.

‘The [subsequent] re-infection rate can be up to 20 per cent.’

These infections are particularly dangerous because the bacteria form ‘biofilms’ — colonies that stick together on surfaces to form impenetrable structures that prevent antibiotics from reaching the bacteria within.

These can be 1,000 times more resistant to antibiotics than free-floating bacteria, say the Spanish research team.

Exacerbating the problem, the surfaces of medical implants are ideal growing conditions for biofilms.

To tackle this problem, the Spanish scientists came up with a brand new approach to treating these infections, which they call the world’s first ‘living medicine’.

It involves modifying the infectious bacteria mycoplasma pneumoniae (which normally causes a type of pneumonia) so that it is not harmful to humans, but also produces two different chemicals that dissolve biofilms and attack the cell walls of the Staph bacteria embedded inside.

Using this bacterial Trojan horse, they managed successfully to cure more than 80 per cent of lab mice that had infected implants, simply by injecting it under their skin, according to a report in the journal Molecular Systems Biology.

The researchers now plan to use the modified bacteria to treat biofilms in hospital patients’ breathing tubes, and expect to start clinical trials in 2023.

But solutions don’t always have to be new, suggest researchers at the University of Warwick, who trialled a concoction to defeat drug-resistant biofilms that was first formulated 1,000 years ago.

Called Bald’s Eyesalve, it is made from onion, garlic, wine and bile salts (manufactured by the liver from cholesterol to break down fats in our diet) and was used to treat eye infections.

The 10th century Bald’s Leechbook, a handwritten, leather-bound text, held in the British Library and considered one of the earliest English medical textbooks, recommends that it be applied to the eye ‘at night with a feather’.

But last year, the Warwick researchers reported that the eyesalve also works effectively against five strains of bacteria that cause biofilm infections: Acinetobacter baumannii, Stenotrophomonas maltophilia, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes.

While allicin, the active ingredient in garlic, can be effective against various bacteria, it doesn’t work against biofilms on its own. It is the winning combination of the other ingredients which makes the salve so effective, together breaking down the biofilm defence, say the researchers.

Last October, the team reported that laboratory tests indicate that the medieval remedy does not damage skin or eye tissue when applied directly to treat infections.

They added that it may, in future, be developed to treat infected wounds, such as diabetic foot and leg ulcers.

Dr Freya Harrison, the University of Warwick scientist who led the research, says the eyesalve could point the way ahead for future bacteria-killing research.

‘Most antibiotics that we use today are derived from natural compounds, but our work highlights the need to explore not only single compounds but mixtures of natural products for treating biofilm infections,’ she says.

‘Future discovery could be enhanced by studying combinations of ingredients, rather than single plants or compounds.’