A 10-year-old child is prescribed gentamicin to treat a diabetic foot infection. Which condition would increase the risk of ototoxicity with aminoglycosides?

• A. Mitochondrial mutation
• B. Renal impairment
• C. Diabetes
• D. Advanced age

Answer: (A)

Genetic susceptibility drives risk of aminoglycoside-induced ototoxicity. Certain mitochondrial mutations, especially in the mitochondrial 12S rRNA gene, make the mitochondrial ribosome resemble the bacterial ribosome that aminoglycosides target. When the drug binds more readily to these mutated mitochondrial ribosomes in inner ear hair cells, it disrupts mitochondrial protein synthesis, energy production and cell survival, leading to irreversible hearing loss. That genetic predisposition means ototoxicity can occur even at standard antibiotic doses, making a mitochondrial mutation the strongest risk factor in this scenario.

Renal impairment can raise risk by reducing drug clearance and increasing exposure, but it isn’t a genetic predisposition. Diabetes and advanced age are not as specific or strong risk factors for aminoglycoside ototoxicity in this context.