Rapid genetic testing can prevent hearing loss in newborns treated for sepsisJune 14, 2018
More than a million neonatal deaths worldwide each year are estimated to be due to sepsis1. In the UK there are approximately 90,000 admissions to neonatal intensive care units per year. Nearly all these patients receive antibiotic therapy during their hospital stay, but babies with a specific genetic change can suffer irreversible hearing loss as a result. Now, in a collaboration between Manchester-based geneticists and a molecular diagnostics company, a rapid test for distinguishing those infants who will have this adverse reaction to the antibiotic gentamicin has been developed.
Dr John McDermott, from the Manchester Centre for Genomic Medicine, Manchester, UK, will tell the annual conference of the European Society of Human Genetics tomorrow (Saturday) that their simple test for bedside use can produce a result in around 40 minutes. « In the absence of a point of care testing approach we are reliant on core hospital testing facilities, which can take up to three days to provide a result. This is inadequate, considering that life-saving antibiotics need to be given in the first hour of admission, » he says. « Our test, developed together with Genedrive plc, uses a cheek swab and can allow tailored prescribing. We are thus able to avoid the antibiotic-related deafness that can occur in infants with this genetic mutation. »
Although there are several antibiotics that can be used to treat sepsis, the UK National Institute for Health and Care Excellence (NICE) recommends a combination of penicillin and gentamicin because the combination has a narrow spectrum of activity and hence a lower risk that the patient might develop antibiotic resistance. But, in new-borns, a particular mutation in mitochondrial DNA2 that is present in one in every 500 of the population, means that a single dose of gentamicin can cause profound and irreversible hearing loss.
"The development of our test has provided us with an exciting opportunity to explore how genetic information can be used in acutely unwell patients, » says Dr McDermott. « As genomic data become ever more prevalent in the population, studies like this will be essential in establishing how patients, clinicians and healthcare systems respond to genetic information being used to personalise treatment as part of everyday healthcare. »
The collaboration plan to undertake a multi-centre feasibility study introducing the test into several neonatal centres around the UK3. All children admitted to these centres will be tested for the genetic change and antibiotics tailored accordingly. « This represents the first example of a point of care genetic test being used in the acute setting, » Dr McDermott will say. « Acute neonatal disease is hugely distressing for all concerned, and we are delighted to be able to contribute to the safety and efficacy of its treatment. »
Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University in Newcastle, United Kingdom, said: "This study shows us the importance of rapid genetic tests to prevent severe side effects from the use of antibiotics in a small group of sepsis patients who carry a mutation in their DNA. Identifying those patients within an hour can now allow doctors to prescribe alternative drugs in this group of patients, whereas the majority of patients can safely use the standard antibiotics."
1 Sepsis, also referred to as blood poisoning or septicaemia, is a potentially life-threatening condition, triggered by an infection such as pneumonia or a urinary tract infection. In neonates the symptoms of sepsis can include extreme tiredness, mottling of the skin and an abnormally fast breathing rate. It is essential that treatment is started as quickly as possible.
2 DNA found in the mitochondria (organelles within a cell that convert chemical energy from food into a form that cells can use) makes up a small proportion of the total DNA found in cells. It encodes for a very small number of genes and is inherited solely from the mother.
3 The initial study will take place in two large neonatal units in Manchester and Liverpool, and will expand nationwide at a later date.
European Society of Human Genetics
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