New drug combination destroys deadly bacterial infection

A new treatment developed by researchers at Aston University and Birmingham Children’s Hospital has been found to completely kill a bacterial infection that can be deadly to patients with cystic fibrosis and other chronic lung conditions such as bronchiectasis. Their work has been published in the journal Scientific Reports.

Mycobacterium abscessus is a bacterial pathogen from the same family that causes tuberculosis, which causes serious lung infections in people (particularly children) with lung disorders — most notably cystic fibrosis (CF). The infection results in severe decline in lung function — sometimes resulting in death — and can also be deadly if the patient requires a lung transplant, because they are not eligible for surgery if the infection is present. It is also highly drug resistant — currently patients are given a cocktail of antibiotics that causes serious side effects, including severe hearing loss, and often doesn’t result in cure.

The current treatment consists of amoxicillin, which is a widely used broadspectrum antibiotic belonging to the β-lactam class of antibiotic (like penicillin). M. abscessus is resistant to most of this antibiotic class due to the production of the enzyme β-lactamase, which destroys the antibiotics and thus renders them useless. Using a novel FDA-approved β-lactamase inhibitor, known as relebactam, alongside amoxicillin, the team has demonstrated that amoxicillin can be made active against M. abscessus.

Utilising biochemical techniques, the team has shown that relebactam directly inhibits the β-lactamase enzyme produced by M. abscessus, explaining why the use of relebactam results in susceptibility to amoxicillin. With the addition of another, newer β-lactam, imipenem, the researchers could reduce the amounts needed of each drug to inhibit M. abscessus growth.

Testing the new drug combination against samples of M. abscessus taken from 16 infected cystic fibrosis patients, the researchers found that the amounts of amoxicillin-imipenem-relebactam required were low enough to be given safely to patients. Not only was the treatment 100% effective in killing off the infection, it also does not have any side effects, thus ensuring their quality of life and improving survival chances for infected CF patients.

“This new drug combination is a significant step forward for patients with cystic fibrosis that get infected with the deadly Mycobacterium abscessus bacteria,” said Aston University’s Dr Jonathan Cox, leader of the team that discovered the treatment. “Our new drug combination is significantly less toxic than those currently used, and so far we have managed to kill every patient’s bacterial isolate that we have received.

“This shows our drugs, when used in combination, are widely effective and could therefore make a huge difference to people whose treatment options are currently limited.”

With more funding, the next stage of the research will be to test the treatment on more people with CF infected by this bacterium, comparing it to the antibiotics that are currently used. Dr Cox noted, “Because amoxicillin is already widely available and imipenem-relebactam has just been approved for use by the Food and Drug Administration (FDA) in the US, these drugs are already available to clinicians. We therefore hope to start treating patients as soon as possible.”

Dr Paula Sommer, Head of Research at the Cystic Fibrosis Trust, added, “Mycobacterium abscessus, also known as NTM, is the most feared infection a person with cystic fibrosis can develop. Taking drugs to treat NTM can add to an already significant regime of daily treatments and take up to a year to clear infections. We look forward to a time when effective, short courses of treatment are available to treat NTM.”

Image credit: ©stock.adobe.com/au/familylifestyle

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