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Common Antibiotic Neosporin May Shield Against Viral Respiratory Infections
The COVID-19 pandemic focused attention on viral respiratory infections and how they can be prevented and treated.
With effective vaccines against SARS-CoV-2 — the virus that causes COVID-19 — severe disease is less common than it was at the start of the pandemic, but there are still few effective treatments for this and other viral respiratory infections.
Currently, doctors use antivirals to try and prevent progression of these infections, with monoclonal antibodies and convalescent plasma for combating severe disease.
Now, a study led by researchers from Yale has found that a cheap, widely available antibiotic might reduce the risk of severe disease from viral respiratory infections.
The study found that neomycin, applied inside the nose, caused a strong immune response in mice and hamsters which protected against infection with both SARS-CoV-2 and influenza A.
And a small group of healthy people treated with a common nasal ointment containing neomycin — Neosporin — showed a similar immune response.
The study is published in PNAS.
William Schaffner, MD, professor of preventive medicine in the Department of Health Policy, and professor of medicine in the Division of Infectious Diseases at Vanderbilt University Medical Center, Nashville, TN, not involved in the study, commented on the findings for Medical News Today:
"This is a very provocative study. Clearly, there is an urgent need for better ways both to prevent and to treat serious respiratory infections. This series of early studies suggests that non-specific immune stimulation by an over-the-counter antibiotic ointment could protect the mucus membranes of the nose from viral infection. This is a fascinating counter-intuitive concept that is worth pursuing further."
Antibiotics are drugs that kill bacteria and/or prevent them from multiplying. They are used to treat bacterial infections inside the body and also as topical treatments for infections of the skin.
Neomycin is an aminoglycoside antibiotic. People take it orally for infections in the digestive tract, or can use it as a topical ointment, neosporin.
Neosporin ointment, which contains neomycin and two other antibiotics, is used to prevent infection in minor cuts and burns, for bacterial infections of the nose, and for management of nosebleeds.
The researchers in this study investigated whether intranasal application of neomycin evoked antiviral protection against SARS-CoV-2 and influenza A in the upper respiratory tract of mice and whether it prevented transmission of SARS-CoV-2 in hamsters.
Jonathan Stoye, PhD, virologist and principal group leader at the Francis Crick Institute in London, United Kingdom, not involved in this research, explained to MNT:
"The concept of preventing virus infection by stimulating natural antiviral immunity has enormous appeal."
First, the researchers treated mice with a single dose of 2 milligrams (mg) neomycin sulfate as 10 microliters (μL) of neomycin solution per nostril. They euthanized mice on days 1, 3, 5, and 7 after neomycin treatment and collected nasal tissue for analysis.
From day 1, the neomycin-treated mice had significantly increased levels of interferon-stimulated gene (ISG) expression — an immune response that is effective against viruses — compared with controls.
The researchers then infected neomycin-treated transgenic (genetically engineered) mice with different strains of SARS-CoV-2.
The mice did not show the usual signs of infection, such as weight loss, and most survived the infection, whereas the control mice did not. Nasal cells from the neomycin-treated mice showed significantly lower levels of viral replication than those of control mice.
Neomycin-treated mice had a similar increase in resistance to influenza A infection.
The researchers treated Syrian hamsters with intranasal neomycin (5 mg) then housed them with hamsters that had been infected 24 hours earlier with SARS-CoV-2. One day later, only half of the neomycin-treated hamsters had any signs of infection.
"This early-stage research in several rodent models identifies one compound, neomycin, that appears to have [antiviral] activity," Stoye told MNT.
However, Schaffner cautioned that findings in rodents might not be applicable to people. "It is a long jump from animal studies to use in humans. This study represents the first steps in a long journey," he said.
The researchers then conducted a small, double-blind pilot study in people. A group of 12 healthy volunteers was treated with Neosporin ointment, which contains neomycin sulfate, bacitracin, and polymyxin B as its active ingredients.
They applied the ointment inside their nostrils using a cotton swab twice a day. Control volunteers applied petroleum jelly (Vaseline) in the same way.
When their immune responses were tested on days 4, 8 and 12 of the trial, the Neosporin-treated group had a much higher ISG response rate than the controls.
"Although an immune response in human volunteers was elicited by the intranasal application of Neosporin ointment, whether this would prevent or treat viral infections in people will have to be demonstrated in a prospective, double-blind trial in a large group of volunteers," cautioned Schaffner.
"Early results always are exciting, but much more work is needed before we can consider this for clinical application," Schaffner noted.
Using antivirals to treat infections can drive the development of resistant strains as respiratory viruses mutate rapidly, so the researchers suggest that stimulating the innate immune response using antibiotics could be an effective alternative treatment.
The researchers also point out that neomycin is cheap, readily available, and easy to administer intranasally.
However, both Schaffner and Stoye had concerns about using neomycin in this way.
Schaffner told us:
"In order to prevent SARS-CoV-2 or any respiratory viral infection, patients likely would have to apply the Neosporin ointment to the nose for very long periods of time. Whether persons would be compliant with such a regimen would have to be determined. Also, the safety of such prolonged application of the ointment to the nasal mucus membranes would have to be established."
He also highlighted the risks of using any antibiotic for prolonged periods: "In addition, there is the concern that the widespread and prolonged use of the antibiotic ointment could provoke the development of antibiotic resistance of the usual bacterial population of the nose and throat. If so, this would be a notable limitation."
While welcoming the study, Stoye called for further research into the treatment. "Much more work will be required to determine how it works, whether it is protective in humans and whether it would be safe to use on the population level," he noted.
Could Viruses Called Bacteriophages Be The Answer To The Antibiotic Crisis?
Surgeon Gabriel Weston visited the Eliava Institute in the former Soviet Republic of Georgia to find out more about a decades-old treatment that could prove vital in the battle against drug resistant superbugs.
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Our generation has been lucky enough to live through a golden age in medicine – the age of antibiotics, where drugs to kill bacterial infections off quickly are readily available. Now, though, growing numbers of bacteria are becoming resistant to our most powerful drugs, evolving into new strains – often called 'superbugs' – that we can no longer kill. Already drug resistance kills over 700,000 people globally every year and if we fail to tackle the problem it could cause an extra 10 million deaths a year by 2050.
New antibiotic drugs are proving difficult to find – but there is a completely different approach to killing bacteria that may prove vital in saving us from infections: using viruses.
'Phage therapy' uses naturally occurring viruses called bacteriophages (from the Greek meaning 'bacteria-eaters') to fight bacteria. The phages used in this therapy are harmless to people but lethal to bacteria. When a phage encounters its prey, it latches onto the outside and injects its own DNA inside the cell. This reproduces inside the bacterium and then the 'daughter phages' burst through the cell walls, before latching onto more bacteria and repeating the cycle until all the bacteria have been killed – and the infection has been dealt with.
Phages were first discovered by two different scientists – the Briton Frederick Twort in 1915 and the French-Canadian Felix d'Herelle in 1917, but it was d'Herelle who really pioneered phage therapy. For a while it was pursued in the west, but when antibiotics were discovered and came into common use in the 1940s phage therapy was abandoned and quickly forgotten.
Behind the iron curtain however, in Stalin's Soviet Republic, access to antibiotics was limited, so phage therapy continued and a phage therapy centre was founded in Tbilisi, Georgia, by a scientist named George Eliava. Tragically Eliava was killed in 1937 during Stalin's purges, but not before he had made Tbilisi a leading centre for phage research.
One of the most fascinating areas of the Eliava Institute are the phage laboratories where different phages are identified and developed into treatments for a vast range of infections. Unlike antibiotics, which target a broad range of bacteria, each phage kills only one type or strain, so doctors here begin by taking bacterial samples from patients and finding a phage from the lab that can kill that particular bacteria.
One of the great advantages with this therapy is that it's much harder for bacteria to develop resistance to phages due to their diversity, their ability to evolve and their sheer abundance. Bacteriophages are actually the most abundant life form on earth – there are far more phages than there are stars in the visible universe. So if bacteria evolve to resist a particular phage, the scientists at the Eliava simply turn to their extensive phage library, or to nature, to find another. They also create what are known as 'phage cocktails' – mixtures of different phages that attack bacteria from different angles and make it much more difficult for them to develop resistance.
Currently phage therapy is not approved or regulated in the west and this is the next big challenge. The good news is that the first large scale, western standard clinical trials have now begun, so hopefully in future we see this incredible 100 year old therapy returning to Europe to help us beat the superbugs.
How A Common Antibiotic Ointment Could Help Fight Viruses
Antibiotics are used to fight bacterial infections, and unless there is a risk that a viral infection will lead to more problems, antibiotics are not often recommended for other illnesses. However, a new study has suggestd that a general antibiotic called neomycin could help prevent viral infections in the respiratory system, when the antibiotic is applied topically to the inside of the nose. The researchers determined that the antibiotic application activated interferon-stimulated genes (ISGs), causing an immune response in an animal model and healthy humans. The findings have been reported in the Proceedings of the National Academy of Sciences (PNAS).
"This is an exciting finding, that a cheap, over-the-counter, antibiotic ointment can stimulate the human body to activate an antiviral response," said co-senior study author Akiko Iwasaki, a Professor at Yale School of Medicine and Howard Hughes Medical Institute investigator.
In this work, mice that were exposed to either the SARS-CoV-2 virus or a virulent strain of influenza A were also given neomycin intranasally. A strong ISG response was triggered in both cases. Contact transmission of SARS-CoV-2 (the virus that causes COVID-19) was reduced in a hamster model that was treated intranasally with neomycin as well.
"Our work supports both preventative and therapeutic actions of neomycin against viral diseases in animal models, and shows effective blocking of infection and transmission," said Iwasaki.
There are often few drugs to reliably and effectively treat viral infections. They are typically monoclonal antibodies or plasma therapies, which can be expensive. But the application of a topical antibiotic may be a new and inexpensive way to prevent respiratory infections before they happen.
"Our findings suggest that we might be able to optimize this cheap and generic antibiotic to prevent viral diseases and their spread in human populations, especially in global communities with limited resources," Iwasaki said. "This approach, because it is host-directed, should work no matter what the virus is."
The researchers also confirmed these findings in a small group of people. When Neosporin, which contains Neomycin, was applied to healthy human noses, ISGs were strongly activated in some of the volunteers. However, this work will have to be confirmed in a larger cohort before a recommendation can be reliably made that people should use antibiotic ointment in their noses to prevent viral infections.
Sources: Yale University, Proceedings of the National Academy of Sciences
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