Alison Pic 05

Preventing gentamicin-induced hearing loss in neonates

Gentamicin is an aminoglycoside antibiotic that was discovered in the early 1960s. Its low cost and efficacy against Gram-negative bacteria (including many multidrug resistant ones), has made it a popular choice for treating serious infections and sepsis in adults and children. However, aminoglycoside antibiotics can be nephrotoxic and ototoxic. Although the nephrotoxicity seems to cause only mild renal impairment that is almost always reversible, the damage to the ear seems to be largely irreversible. The damage to the ear can occur in two ways: (1) vestibular toxicity destroys the vestibular system, which is responsible for our sense of balance and motion, causing chronic vertigo; and (2) cochleotoxicity, which destroys the hair cells causing hearing loss. Treatment with gentamicin is therefore carefully monitored with the assessment of serum levels allowing careful control of the dosage regimen. In the 1990s, it became apparent that a mitochondrial DNA mutation (m.1555A→G) dramatically increased the susceptibility of carriers to aminoglycoside-dependent hearing loss, which can be profound even after very limited exposure and when drug levels have been kept within the therapeutic range. In adults, hearing loss has been thought of as an unavoidable possible side-effect when trying to save a life from serious infection. However, for the many babies treated with gentamicin (approximately 90 000 per year in the UK alone), the potential consequences are devastating, as the lack of hearing means that the development of speech is extremely difficult. Invasive bacterial infection can affect up to 25% of very low birth weight babies, with unspecific symptoms and the possibility of rapid progression to a high risk of morbidity and mortality. Hence, in the presence of risk factors for – or any suspicion of – infection, antibiotic therapy is started at birth or within the hour of a baby arriving at the neonatal intensive care unit. The prevalence of the m.1555A→G mutation has been found to be 1 in 500 in European children, but currently there is not enough time for genetic screening to take place before commencement of antibiotics. Recently, however, a consortium (led by Professor Bill Newman, professor of Translational Genomic Medicine at the University of Manchester and a consultant at Manchester University NHS Foundation Trust, and including partners from Liverpool and Manchester Neonatal Intensive Care Units) has received funding to develop a new point-of-care test that will allow rapid identification of children with the mutation and so save their hearing by avoiding the use of aminoglycoside antibiotics. Needless to say, such a test will be greatly welcomed by parents, removing one very difficult decision at a time of great stress.