ANCIENT SOLUTIONS FOR MODERN PROBLEMS: FIGHTING ANTIBIOTIC RESISTANCE WITH A 10TH CENTURY REMEDY

ANTIBIOTIC RESISTANCE IS A SERIOUS THREAT TO MODERN MEDICINE. HOW CAN AN OLD ENGLISH MEDICAL TEXT CHANGE THE GAME?

Though most people think of leeches and plagues when they think of medieval medicine, we may have to reconsider our old biases. With Infectious bacteria outmaneuvering the antibiotic drugs humans have designed to kill them, we are running out of ways to cure infections. This phenomenon, known as “antibiotic resistance,” is predicted to kill up to 10 million people per year by 2050 if we fail to find new solutions. As a result, scientists are now looking to the past to solve this modern problem.

Bald’s Leechbook is an Old English medical text from the 9th or 10th century.

One relevant or prominent or well known example is MRSA (methicillin-resistant Staphylococcus aureus). Methicillin was once the preeminent antibiotic against several common types of bacteria, but it is now rarely used as the bacteria have evolved resistance to methicillin treatment.

Infection by MRSA is one of the biggest problems in antibiotic resistance. MRSA causes chronic infections that are common in hospitals, nursing homes, prisons, day cares, and other places where injury and close contact between people are common. As a result, scientists and doctors are working together to develop new antibiotics, as well as other, more out-of-the-box treatment options, for MRSA and other similar antibiotic resistant bacteria.

The bacteria family that evolved the dangerous antibiotic resistant strain, MRSA, actually resides in the skin microbiomes of most people. As long as there is a good microbial balance and the bacteria stays in the right locations in the body, aka the outside of the body, it has no effect. However, if S. aureus enters the tissues through a wound or other means, it becomes harmful and needs antibiotic treatment just like an ear infection or strep throat.

HOW CAN A COMMON MICROBE CAUSE SUCH A BIG ISSUE?

When the infecting S. aureus strain is antibiotic resistant, MRSA infection develops quickly and causes severe symptoms if not treated efficiently. In the worst case scenario, infection can spread via the bloodstream and invade the entire body, leading to multi-organ failure and death through a process known as septic shock.

While MRSA is the leading cause of infections acquired while in the hospital, it can sometimes be treated with a mix of antibiotics. Two main drugs, vancomycin and linezolid, are effective against the majority of MRSA infections, but there is an increasing number of MRSA strains that are evolving resistance against these antibiotics as well.

Additionally, S. aureus can create a biofilm at the site of infection, which is a collection of bacteria embedded in a slimy matrix that sticks to the surrounding tissue. Treatment of MRSA biofilms can involve taking antibiotics at 100-1000 times higher strength than is typically given, and antibiotic use can last for three months or longer to fully clear the infection. On top of that, antibiotics can cause long-lasting effects on our gut microbiome. One study suggests that our microbiomes could take over a year to go back to normal after antibiotic treatment. MRSA infection is just example of the severe problems caused by antibiotic resistance, and its prevalence and severity highlight the importance of finding new treatment options.

NEW TREATMENT OPTIONS MIGHT COME FROM OLD SOURCES

A group of researchers in the United Kingdom found a promising recipe in an early medical text titled “Bard’s Leechbook” from over 1,000 years ago. This book contains a treatment for eye lumps entitled “Bald’s eyesalve” that may be the newest innovation in the fight against antibiotic resistance. The eye lumps addressed in the recipe are likely what we know today as “styes,” which are infections of the eyelash follicle typically caused by the same bacteria responsible for MRSA infection: S. aureus. This similarity led the researchers to study the old recipe: combine garlic, wine, “oxgall” (stomach bile of a cow), and “cropleac” (an ancient relative of onion) in a bronze vessel for nine days to create a brown balm that can be applied to the offending lump to eliminate S. aureus infection.

The list of ingredients seemed promising to the researchers in their search for MRSA treatment. Garlic and cropleac, or onions, contain antimicrobial compounds that prevent biofilm formation. Bile effectively prevents overgrowth of bacteria, since that is its role in the small intestine. The wine either serves as a source of antimicrobial small molecules, or it may just be the right acidity to extract other compounds created in the salve.

In the Early Medieval period, mixing the salve in a bronze vessel ensured that the salve was stored in a relatively clean container: copper salts prevent bacterial growth and would have ensured that bacteria did not grow in the salve as it sat over several days. It’s amazing what doctors were able to discover in times before germ theory and microscopes.

A scientist holds a lab-made vial of Bald’s eyesalve.

The scientists rigorously tested this formula. They discovered that Bald’s salve contains antimicrobial properties and more importantly is also able to kill MRSA and other antibiotic-resistant bacteria more effectively than the last-line antibiotic defense against MRSA, vancomycin. Using the more modern leek or onion in place of cropleac, the mixture of all listed ingredients was necessary for full effectiveness against MRSA. When testing combinations that left out one ingredient each, the salve did not achieve the same result.

In its complete form, this salve managed to efficiently kill S. aureus in a petri dish. But even more importantly, Bald’s salve was even more effective than the antibiotic vancomycin at penetrating a thick bacterial biofilm and resolving MRSA infection in a synthetic wound. This more accurately represents what might happen in a real infection. What is more, when investigating the salve’s potency against other bacteria, they found that it kills Neisseria gonorrheae, a multi-drug-resistant bacteria that is a major cause of childhood blindness.

CAN THIS BE USED TO TREAT PEOPLE NOW?

Just because a formula kills harmful bacteria does not always mean it is safe to use on humans, especially on delicate wounds. To test the real-world application of Bald’s eye salve, the researchers applied it to both bovine eyes and laboratory-grown human skin cells. Minor irritation occurred for a short time at the treatment sites, but it was mild enough for the researchers to propose safe testing on real-life humans, which will likely begin soon.

Given the importance of discovering new solutions to fight bacterial infection in the face of antibiotic resistance, the results of studying Bald’s eye salve are a big step in the right direction. Not only does the salve itself serve as a potential MRSA treatment, it also highlights the importance of looking at emergent properties for drug development. While the line between medical and mystical healing was blurred in Europe’s Early Medieval period, this eye salve contains biologically sound ingredients for curing bacterial infections and provides modern researchers a solid candidate to further the fight against antibiotic resistance.

REFERENCES

1. de Kraker M. E. A. et al. “Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050?” PLoS Med. (2016)

2. Palleja A. et al., “Recovery of gut microbiota of healthy adults following antibiotic exposure.” Nat Microbiol. (2018)

3. Harrison F. et al. “A 1,000 year old antimicrobial remedy with anti staphylococcal activity.” Mbio. (2015)

4. Anonye B. O. et al. “The safety profile of Bald’s eye salve for the treatment of bacterial infections.” Scientific Reports. (2020)

5. Furner-Pardoe J. et al. “Anti-biofilm efficacy of a medieval treatment for bacterial infection requires the combination of multiple ingredients.” Scientific Reports. (2020)

6. Sissons R. “1,000-year-old onion and garlic eye remedy kills MRSA.” BBC News. (2015)