Foundations · Year 1 · from Foundations
Case 2: Aminoglycoside-Induced Ototoxicity (Ribosomal Inhibition)
Clinical Image
Source: Wikipedia - Aminoglycoside - CC BY-SA 3.0
Case Presentation
A 68-year-old man with infective endocarditis due to Enterococcus faecalis is treated with 6 weeks of ampicillin plus gentamicin. During week 4, he reports progressive hearing loss and tinnitus, initially attributed to his age and illness. Formal audiometry reveals bilateral high-frequency sensorineural hearing loss. Gentamicin trough levels are checked and found to be elevated. The antibiotic is discontinued, but hearing loss persists and proves to be permanent. The mechanism is explained: aminoglycosides bind to the 30S ribosomal subunit, causing misreading of the genetic code and premature termination. While this preferentially affects bacterial ribosomes (explaining the antibiotic effect), human mitochondrial ribosomes are more similar to bacterial ribosomes than cytoplasmic ribosomes are. Individuals with certain mitochondrial DNA mutations (m.1555A>G in 12S rRNA) are particularly susceptible to aminoglycoside ototoxicity, even with single doses. Hair cells of the inner ear depend heavily on mitochondrial function and, once damaged, cannot regenerate. Genetic testing reveals he carries the m.1555A>G mutation. His family members are counseled to avoid aminoglycosides.
Key Learning Points
- Aminoglycosides bind the 30S ribosomal subunit decoding site, causing misreading and premature termination; they preferentially affect bacterial ribosomes but can also impact mitochondrial ribosomes
- Human mitochondrial ribosomes resemble bacterial 70S ribosomes more than cytoplasmic 80S ribosomes, making mitochondria vulnerable to some antibiotics; the m.1555A>G mutation in mitochondrial 12S rRNA increases this vulnerability
- Ototoxicity from aminoglycosides affects cochlear hair cells which have high metabolic demands and cannot regenerate; the hearing loss is typically irreversible