A guideline from the UK's pharmacogenomics centre of excellence, published in the British Journal of Clinical Pharmacology on 29 July, addresses the mitochondrial MT-RNR1 variants m.1555A>G, m.1494C>T and m.1095T>C. Present in about 1 in 330 people across populations, they predispose to permanent sensorineural hearing loss after aminoglycoside exposure — sometimes after a single dose, and at normal therapeutic levels, so drug monitoring does not protect against it.
The guideline recommends avoiding aminoglycosides in anyone found to carry a variant, at any detectable level. About a fifth of aminoglycoside use is predictable, which is where pre-emptive testing makes sense. In England, laboratory testing is commissioned nationally and some neonatal units use point-of-care tests. Crucially, where a result is not available and the need is urgent, treatment should not be delayed.
For prescribers the change is to ask about maternal-line family history of deafness after antibiotics, and to use testing where the aminoglycoside can wait. MT-RNR1 testing is not routinely available in most Indian settings; the family-history question costs nothing.
- Avoid aminoglycosides in anyone known to carry an MT-RNR1 risk variant.
- Ask about hearing loss after antibiotics in the maternal family line before a planned aminoglycoside course.
- Consider pre-emptive MT-RNR1 testing where aminoglycoside use is predictable and testing is available.
- Never delay an aminoglycoside in sepsis while waiting for a genotype result.
- Therapeutic drug monitoring does not prevent this form of ototoxicity.
Why it matters
Level monitoring protects kidneys, not the ears of variant carriers, for whom one dose can mean lifelong deafness.
Don't overread it
This is a UK guideline recommending targeted testing, not universal screening before every dose.
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