Gentamicin is an antibiotic used to treat many different types of infections, and is commonly used in neonatal intensive care units where time is of the essence to prevent and manage sepsis. A potential adverse side effect of gentamicin is ototoxicity, which in some cases can lead to permanent hearing loss, and genetic variations can make some patients more susceptible to severe side effects. Currently available genetic tests to detect these variations can take several days to complete, which is not feasible in an acute setting. Now, University of Manchester researchers have developed and successfully piloted a rapid bedside test that provides results in just 25 minutes and could potentially prevent hearing loss for hundreds of babies each year in the UK alone.
The testing platform, developed at the University of Manchester-based start-up Genedrive, is a rapid thermocycling instrument that performs loop-mediated isothermal amplification followed by fluorescent hybridization probe-based melt analysis for detection of the m.1555A>G variant of the MT-RNR1 gene, which makes patients more susceptible to hearing loss from gentamicin treatment. The point-of-care test can be performed at the patient’s bedside, using a buccal swab sample, and delivers results in about 25 minutes. If a patient is found to have the m.1555A>G variant, they can then be prescribed an alternative antibiotic.
The platform was piloted at two large NICUs in the United Kingdom in 2020, with a total of 424 newborns successfully tested for the variant. Of this group, three newborns with the variant were identified, which was later confirmed by Sanger sequencing. The assay was found to have an analytical sensitivity of 100%, a specificity of 99.2% and an accuracy of 99.2%, with five false positive results and no false negatives. The testing process could be successfully integrated into normal clinical practice without causing any delay in time to treatment. The results of this trial were published in JAMA Pediatrics.
“It’s a great example of using human genetics to guide specific therapy, which is now taking front and center in clinical management globally,” said Genedrive CEO David Budd. “The application of Genedrive’s technology shows how a rapid, affordable, point-of-care test could impact patients’ treatment and quality of life across this as well as a wide range of fields.”
The Genedrive system is now fully CE certified to be used in a clinical setting, and about 300 nurses are now being trained to use the platform across several UK hospitals. More than 100,000 infants are treated with gentamicin or other aminoglycoside antibiotics in the UK each year; as approximately 1 in 500 patients carry the m.1555A>G variant, the technology has the potential to prevent hearing loss in hundreds of infants nationally.