Aminoglycoside-Induced Cochleotoxicity: A Review

Abstract

Aminoglycoside antibiotics are used as prophylaxis, or urgent treatment, for many life-threatening bacterial infections, including tuberculosis, sepsis, respiratory infections in cystic fibrosis, complex urinary tract infections and endocarditis. Although aminoglycosides are clinically-essential antibiotics, the mechanisms underlying their selective toxicity to the kidney and inner ear continue to be unraveled despite more than 70 years of investigation. The following mechanisms each contribute to aminoglycoside-induced toxicity after systemic administration: (1) drug trafficking across endothelial and epithelial barrier layers; (2) sensory cell uptake of these drugs; and (3) disruption of intracellular physiological pathways. Specific factors can increase the risk of drug-induced toxicity, including sustained exposure to higher levels of ambient sound, and selected therapeutic agents such as loop diuretics and glycopeptides. Serious bacterial infections (requiring life-saving aminoglycoside treatment) induce systemic inflammatory responses that also potentiate the degree of ototoxicity and permanent hearing loss. We discuss prospective clinical strategies to protect auditory and vestibular function from aminoglycoside ototoxicity, including reduced cochlear or sensory cell uptake of aminoglycosides, and otoprotection by ameliorating intracellular cytotoxicity.

Succinic Semialdehyde Dehydrogenase Deficiency: An Update

“…For gentamycin, clinical trials have produced variable results [142,143,144,145], as it does not seem to be efficient for all patients. Long-term administration of aminoglycosides is not feasible due to their strong side effects such as ototoxicity and kidney damage [146,147]. The varying effects of gentamicin may be explained by the fact that gentamicin is not a pure substance, but is composed of different major and minor gentamicin components.…”

Pediatric Ototoxicity: Current Trends and Management

“…Many bacterial infections (including tuberculosis, sepsis in newborns, pulmonary infections stemming from cystic fibrosis, and infections secondary to heart conditions) are treated with aminoglycoside antibiotics. 12,13 Aminoglycosides may be used to treat acute disease, or may be used as prophylaxis against opportunistic infections; they are widely used around the world, are inexpensive, and highly effective at treating a wide range of gram-negative bacteria. 13 With increasing cumulative dose of aminoglycoside antibiotics, risk of hearing loss increases.…”

Mitochondria-homing peptide functionalized nanoparticles performing dual extracellular/intracellular roles to inhibit aminoglycosides induced ototoxicity

“…Aminoglycosides induced irreversible ototoxicity represents one of the prevalence forms in drug-related hearing loss even though they are clinically indispensable for the treatment of some severe infections [1][2][3]. Although lots of efforts related to preventative options via monitoring of their dose and treatment duration restrict the occurrence, the prevalence of ototoxicity following aminoglycosides exposure is still estimated in the range of 2-25% [2].…”