A collaboration between the UK’s National Institute for Health Research and the molecular diagnostics company Genedrive plc, Manchester, UK, has developed a rapid test for identifying infants with a specific genetic mutation of the mitochondrial DNA responsible for irreversible hearing loss as an adverse reaction to the antibiotic gentamicin.

Sepsis is believed to be responsible for more than 1 million neonatal deaths worldwide each year. It is essential for clinicians to initiate antibiotic treatment within the first hour after admission. For this reason, nearly all of the approximately 90,000 babies admitted to neonatal intensive care units in the UK each year receive a combination of penicillin and gentamicin, following the recommendations of the UK’s National Institute for Health and Care Excellence (NICE). This combination therapy lowers the risk of developing antibiotic resistance; however, for one in every 500 newborns who carry a specific genetic mutation, a single dose of gentamicin can cause profound and irreversible hearing loss.

Current lab-based genetic tests are not able to return actionable results within the 1-hour timeframe for treatment initiation. By contrast, the Genedrive test is a simple bedside test that produces genetic results in around 40 minutes, facilitating the use of alternative antibiotics for infants identified as genetically predisposed to hearing loss as an adverse reaction to gentamicin.

John McDermott, MBChB, Manchester Center for Genomic Medicine.

John McDermott, MBChB, Manchester Center for Genomic Medicine.

“In the absence of a point-of-care testing approach, we are reliant on core hospital testing facilities, which can take up to 3 days to provide a result. This is inadequate, considering that life-saving antibiotics need to be given in the first hour of admission,” says John McDermott, MBChB, of the Manchester Center for Genomic Medicine. “Our test, developed together with Genedrive, 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.”

The collaboration plans to undertake a multicenter feasibility study introducing the test into several neonatal centers around the UK, including two large neonatal units in Manchester and Liverpool. All children admitted to these centers will be tested for the genetic alteration and receive antibiotics tailored accordingly.

“The development of our test has provided us with an exciting opportunity to explore how genetic information can be used in acutely unwell patients,” adds 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 personalize treatment as part of everyday healthcare.”

“This represents the first example of a point-of-care genetic test being used in the acute setting,” notes McDermott. “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.”

“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,” says Joris Veltman, professor and director of the institute of genetic medicine at Newcastle University. “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.”

The research was made possible by a multipartner grant from the UK’s National Institute for Health Research, with funding through Action on Hearing Loss. The consortium is led by William Newman, professor of translational genomic medicine at the University of Manchester and consultant at Manchester University NHS Foundation Trust.

“We look forward to working with Genedrive and our colleagues in Manchester and Liverpool to assess the impact of rapid genetic testing as a method of avoiding irreversible hearing loss in babies treated with antibiotics,” says Newman. “Successful implementation would be a first in the integration of a rapid decisionmaking, genetic-based diagnostic in the UK NHS.”

The project represents an important landmark for the Genedrive platform, as it is the first potential application outside of the low- and middle-income markets targeted by the company’s current hepatitis C and tuberculosis programs.

“The application of Genedrive in an urgent healthcare setting is an excellent example of how a rapid, affordable, point-of-care test could impact patients’ treatment and quality of life,” says David Budd, CEO of Genedrive. “The NHS is a huge marketplace and, if adopted, would be the first placement of Genedrive in a developed world healthcare setting. The project is an exciting opportunity to expand the markets in which Genedrive is used.”

To learn more, visit Genedrive.