Genetic Screening Would Prevent Hearing Loss Caused by Antibiotics

Hearing loss caused by a group of antibiotics called aminoglycosides could be prevented if patients were screened for a genetic mutation before treatment.

Hearing loss caused by a group of antibiotics called aminoglycosides could be prevented if patients were screened for a genetic mutation before treatment, say experts in this week’s BMJ.

Aminoglycosides are most useful for the treatment of serious infections, such as septicaemia, complicated urinary tract infections, and tuberculosis.

Their potential for ototoxicity (damage to the ear) is well known, but less well known is that some people have an inherited predisposition that renders them highly sensitive to these effects and can result in severe and permanent hearing loss, write Maria Bitner-Glindzicz and Shamima Rahman at the Institute of Child health in London.

The mutation, known as m.1555A-G is thought to cause up to 5% (1 in 40,000) cases of deafness in children in the UK. This is low compared to other countries. Studies from New Zealand and the US, for example, found between 1 in 206 and 1 in 1,161 positive cases in newborns.

Even in the absence of exposure to aminoglycosides, some families carrying this mutation may also develop deafness, albeit at a later age and with a lower penetrance.

In Spain, for example, 27% of families with at least two deaf individuals were positive for this mutation and everyone with the mutation who was exposed to aminoglycosides became deaf. By the age of 30, the probability of becoming deaf if an individual had received such antibiotics was 96.5% compared with 39.9% if they had never been treated.

Thus aminoglycosides are a major environmental modifier of the m.1555A-G mutation, say the authors.

But is it cost effective to screen for this mutation before aminoglycosides are given? The current cost of testing for this mutation in the UK is about £35 per test. However, this is based on a small number being performed and demand for more tests would reduce the costs. In contrast, the cost to the health service for a child who becomes deaf is estimated to be £61,000 over a lifetime, and an additional £18,000 a year in educational costs.

In the US, the total lifetime cost to society for a child who becomes deaf before acquiring language has been estimated to exceed $1m.

Hearing loss induced by aminoglycosides in individuals with the m.1555A-G mutation is preventable, they say. The mutation is well known among doctors who see patients who already have hearing loss. However, the general medical community is not aware of this susceptibility and that mutation testing is available.

They recommend in this BMJ editorial that the true prevalence of the mutation in the UK be ascertained to determine the cost effectiveness of screening everyone prescribed aminoglycoside antibiotics. In the meantime, patients who are likely to receive multiple courses of aminoglycosides – for example, patients with leukaemia and newborns admitted to special care baby units - should be screened.

Genetic testing needs to be turned around rapidly and consideration should be given to using an alternative antibiotic until the result of genetic testing is known, they conclude.

Source-BMJ
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