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 cystic fibrosis patients and other chronic lung conditions such as bronchiectasis.
The findings, which are published in the journal Scientific Reports, show that scientists from Aston University, Mycobacterial Research Group, combined doses of three antibiotics – amoxicillin and imipenem-relebactam and found it was 100% effective in killing off the infection which is usually extremely difficult to treat in patients with cystic fibrosis. The infection results in severe decline in lung function and sometimes death.
Cystic fibrosis (CF) is a genetic condition affecting more than 10,000 people in the UK (Cystic Fibrosis Trust) and there are more than 70,000 people with the condition worldwide (Cystic Fibrosis Foundation). While bronchiectasis affects 210,000 people in the UK (British Lung Foundation).
Mycobacterium abscessus is a bacterial pathogen from the same family that causes tuberculosis, that causes serious lung infections in people (particularly children) with lung disorders, most notably cystic fibrosis. It is highly drug resistant. Currently patients are given a cocktail of antibiotics that cause serious side effects including severe hearing loss and often doesn’t result in cure.
The researchers used samples of the pathogen taken from 16 infected cystic fibrosis patients and tested the new drug combination to discover how much was required to kill the bacteria. They found the amounts of amoxicillin-imipenem-relebactam required were low enough to be given safely to patients.
Until now Mycobacterium abscessus has been virtually impossible to eradicate in people with cystic fibrosis. It can also be deadly if the patient requires a lung transplant because they are not eligible for surgery if the infection is present.
In the UK, of the 10,000 people living with cystic fibrosis, Mycobacterium abscessus infects 13% of all patients with the condition. This new treatment is advantageous not only because it kills off the infection, but it does not have any side-effects on patients, thus ensuring their quality of life and greatly improving survival chances for infected CF patients.
Dr Jonathan Cox, Lecturer in Microbiology, Aston University and leader of the team that discovered this new treatment said:
“This new drug combination is a significant step forward for patients with cystic fibrosis that get infected with the deadly Mycobacterium abscessus bacteria. 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.”
“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. ”
The findings of this research will impact children being treated for the infection at Birmingham Children’s Hospital – who part funded the research – but it can also be used nationally and further afield.
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 Maya Desai, Consultant in Respiratory Paediatrics, Birmingham Children’s Hospital added: “This exciting development will significantly impact on the care of CF patients globally. It has been possible only with close collaboration between Aston University and Birmingham Children’s Hospital both from a clinical research and financial point of view.”
Dr Paula Sommer, Head of Research at the Cystic Fibrosis Trust said: “It’s exciting that these lab-based studies investigating new antibiotic treatments for M. abscessus infection are showing such promise and adding to our expanding knowledge of this devastating bug.
“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.”
- Journal Scientific Reports, DOI: 10.1038/s41598-020-57844-8
- Link to paper published online
- The treatment consists of Amoxicillin which is a very old, safe, widely used broad spectrum antibiotic belonging to the β-lactam class of antibiotic (like penicillin). Mycobacterium abscessus is resistant to most of this antibiotic class due to the production of an enzyme, β-lactamase, which destroys the antibiotics rendering them useless.
- Using a novel, safe, 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. This is important as it means patients receiving this treatment for M. abscessus lung disease will require less antibiotic, reducing side effects and ultimately better treatment outcomes.
About Aston University
Founded in 1895 and a University since 1966, Aston is a long established university led by its three main beneficiaries – students, business and the professions, and our region and society. Aston University is located in Birmingham and at the heart of a vibrant city and the campus houses all the university’s academic, social and accommodation facilities for our students. Professor Alec Cameron is the Vice-Chancellor & Chief Executive.
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About Birmingham Women’s and Children’s NHS Foundation Trust
Birmingham Women’s and Children’s NHS Foundation Trust (BWC) brings together the very best in paediatric and women’s care in the region and is proud to have many UK and world-leading surgeons, doctors, nurses, midwives and other allied healthcare professionals on our team.
Birmingham Children’s Hospital is the UK’s leading specialist paediatric centre, caring for sick children and young people between 0 and 16 years of age. Based in the heart of the city centre, it is a world leader in some of the most advanced treatments, complex surgical procedures and cutting edge research and development. The hospital is a nationally designated specialist centre for epilepsy surgery and also boasts a paediatric major trauma centre for the West Midlands, a national liver and small bowel transplant centre and a centre of excellence for complex heart conditions, the treatment of burns, cancer and liver and kidney disease. It’s also home to one of the largest Child and Adolescent Mental Health Services in the country, comprising of a dedicated inpatient Eating Disorder Unit and Acute Assessment Unit for regional referrals of children and young people with the most serious of problems (Tier 4) and the Forward Thinking Birmingham community mental health service for 0 to 25 year olds.
Birmingham Women’s Hospital is a centre of excellence, providing a range of specialist health care services to over 50,000 women and their families every year from Birmingham, the West Midlands and beyond. As well as delivering over 8,000 babies a year, it offers a full range of gynaecological, maternity and neonatal care, as well as a comprehensive genetics service, which serves men and women. Its fertility centre is one of the best in the country, while the fetal medicine centre receives regional and national referrals. The hospital is also an international centre for education, research and development with a research budget of over £3 million per year. In April 2016, it was announced as the national miscarriage research centre – the first of its kind in the UK - in partnership with Tommy’s baby charity.