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Comparative ototoxicity of four aminoglycosidic antibiotics during the critical period of cochlear development in the
Insights
Dibekacin showed no ototoxicity in developing rats, while tobramycin and gentamicin had mild to moderate effects. Amikacin caused the most severe cochlear damage, impacting hair cells and auditory function.
Area of Science:
- Ototoxicology
- Developmental Biology
- Pharmacology
Background:
- Aminoglycosides are crucial antibiotics but can cause ototoxicity.
- Understanding the ototoxic potential during critical developmental periods is vital for safety.
Purpose of the Study:
- To compare the ototoxicity of amikacin, dibekacin, gentamicin, and tobramycin.
- To evaluate ototoxicity during the critical period of cochlear development in rats.
Main Methods:
- Newborn rats received daily subcutaneous injections of four aminoglycosides for 8 days.
- Ototoxicity was assessed via cochlear recordings (action potential, cochlear microphonic), surface preparations, and scanning electron microscopy one month post-treatment.
Main Results:
- Dibekacin exhibited no ototoxic effects.
- Tobramycin showed mild ototoxicity (increased N1 latency, OHC stereocilia damage).
- Gentamicin caused moderate ototoxicity (increased CM thresholds, hair cell loss).
- Amikacin resulted in severe ototoxicity (impaired AP/CM thresholds, extensive hair cell loss).
Conclusions:
- Aminoglycoside ototoxicity varies significantly, with dibekacin being the safest during early cochlear development.
- Amikacin poses the highest risk of ototoxicity in developing rat cochleae.
- These findings highlight the importance of considering developmental timing when assessing antibiotic safety.
Abstract:
The comparative ototoxicity of four aminoglycosides (amikacin, dibekacin, gentamicin and tobramycin) was evaluated in the rat during the critical period of cochlear development. Newborn rats received a daily subcutaneous injection of one of the four antibiotics for 8 consecutive days, starting on day 8 after birth (amikacin: 225 mg/kg, dibekacin: 60 mg/kg, gentamicin and tobramycin: 45 mg/kg). Evaluation of ototoxicity was assessed one month after the end of the treatment using cochlear recordings (action potential and cochlear microphonic), surface preparations and scanning electron microscopy. No functional or structural evidence of ototoxicity was found in animals treated with dibekacin. Tobramycin had a weak ototoxic effect characterized by a slight increase in N1 latency and moderate damage to OHC stereocilia (fusion and formation of giant cilia). Gentamicin-treated animals demonstrated more severe evidence of ototoxicity including increased thresholds for CM, and a higher incidence of missing hair cells and damage to OHC stereocilia. The maximal cochlear damage was observed in amikacin-treated animals: both AP and CM thresholds were severely impaired, cell counts and SEM showed extensive loss of hair cells.