Clinicians and nurses in neonatal intensive care units (NICUs) at the University of Manchester NHS Foundation Trust (MFT) are the first in the world to deploy genedrive’s MT-RNR1 ID Kit, a new rapid genetic test in the point of care (POCT) to screen babies for the genetic variant m.1555A>G when admitted with suspected sepsis. Newborns with bacterial infections such as sepsis are commonly prescribed gentamicin, an aminoglycoside antibiotic, however, for babies with an inherited m.1555A>G genetic variant, a single dose of this antibiotic can cause permanent hearing loss.
New clinical trial results demonstrate that Genedrive’s test can detect the presence of the genetic variant in less than half an hour, compared to traditional lab tests, which can take days or weeks to provide results . This historically slow turnaround time meant that this vital patient safety issue could not be determined in an urgent care setting. The rapid result allows clinicians to prescribe alternative antibiotic treatments to newborns with the variant, allowing patients to begin life-saving treatments as soon as possible without risk of hearing loss.
The rollout follows the results of a successful performance trial of the technology in the NICU at Saint Mary’s Hospital in Manchester, part of MFT. Using Genedrive’s test, the Pharmacogenetics to Avoid the Loss of Hearing (PALOH) study – funded in part by the NIHR Manchester Biomedical Research Center (BRC) – examined 751 neonates admitted to NICU for MT-RNR1 genetic variant known as m. 1555A>G, which can deliver results to clinicians in 26 minutes. This information was used to guide prescribing decisions, with babies at risk of antibiotic-induced hearing loss being prescribed an alternative antibiotic.
Prior to using the genedrive test, clinicians had no way of knowing if their newborn had the m.1555A>G variant before prescribing life-saving antibiotics, as existing genotyping technology involves time-consuming laboratory testing. In cases of early neonatal infection, National Institute for Health and Care Excellence (NICE) guidelines state that antibiotic therapy should be started within one hour of the decision to treat with antibiotics, and any delay could be fatal. Thus, clinicians have until now been forced to make prescribing decisions without this genetic information. Genedrive’s test and instrument enabled this, providing clinicians with genetic information in a clinically relevant timeframe. This has the potential to save more than 14,000 newborn babies from permanent hearing loss worldwide each year.
Despite the risk of hearing loss in patients with the m.1555A>G genetic variant, gentamicin is the preferred and recommended antibiotic treatment for neonatal sepsis. This is because alternative broad-spectrum antibiotics such as cephalosporins risk the development of antibiotic-resistant organisms. About 1 in 500 babies carries the m.1555A>G genetic variant.
In non-acute clinical cases, guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the UK Medicines and Healthcare Regulatory Agency (MHRA) already recommend that genetic testing be carried out and that people with the m.1555A>G variant do not. receive aminoglycoside antibiotics, unless the risk of permanent hearing loss is outweighed by the severity of the infection. Thanks to Genedrive’s technology, this informed decision-making is now also available to clinicians working in acute NICU environments.
We have known about the link between m.1555A>G and profound deafness for some time, but there is no way to do a genetic test at the bedside of a patient in less than an hour. Time is running out for clinicians treating newborns with sepsis – they don’t have the luxury of waiting days or weeks for the results of a genetic test. We had seen the valuable work Genedrive was doing testing other genetic variants, and we were eager to explore how its technology could help our NICU nurses and consultants.”
Professor Bill Newman, Genomic Medicine Consultant, MFT
Professor Newman, who is also the Associate Head of Genomics Solutions for Manchester BRC’s Hearing Health Theme, added; “During the trial, genedrive’s rapid point-of-care test provided our clinicians with vital information when they needed it. They no longer had to make prescribing decisions in the dark, and they no longer had the enigma of knowing that some of their patients might develop profound hearing loss after treatment with routine antibiotics. Importantly, Genedrive delivers results in less than 30 minutes, which means treatment can begin within an hour, which is critical in these cases.
MFT is currently rolling out the Genedrive antibiotic-induced hearing loss test to three of its NICUs to begin with, with further rollouts planned. The trust’s first sites to implement the technology include Saint Mary’s Hospital and Wythenshawe Hospital. The Genedrive MT-RNR1 test (test) uses cells taken from a swab taken from the inside of the patient’s cheek. In preclinical validation, the Genedrive platform demonstrated 100% assay sensitivity and 100% specificity. During the PALOH trial, the platform demonstrated true analytical sensitivity of 100%, specificity of 99.2%, and accuracy of 99.2%.
The PALOH study was the first time that molecular diagnostics had been used in a neonatal emergency care setting. With Genedrive’s technology, clinicians have life-changing genetic information at their fingertips. Knowing whether a patient has the m.1555A>G genetic change is essential for making informed prescribing decisions, but in emergency situations doctors cannot wait for lab results. We are delighted with the deployment of our technology in Manchester and the UK, and the potential this has to save thousands of babies from hearing loss each year.
David Budd, CEO, Genedrive
Manchester University NHS Foundation Trust (MFT)