Related Experiment Videos
Aminoglycoside-induced ototoxicity
P J Govaerts1, J Claes, P H van de Heyning
1Department of Otorhinolaryngology, University of Antwerp, Wilrijk, Belgium.
Abstract:
One of the major side effects of aminoglycoside antibiotics (AG) is ototoxicity. The authors review the literature revealing many controversies on every aspect of this side-effect. Although epidemiological studies have to face the problem of reliable evaluation techniques, the incidence of cochleo- and vestibulotoxic side-effects has been estimated at 7.5% for each. Netilmicin appears to be less ototoxic. No definite risk factors can be proposed, although age, length of therapy, bacteremia, fever, liver and renal dysfunction are probably very important parameters. Most pathological changes at the cochlear level follow a clear spatial sequence, showing unspecific, degenerative lesions, involving every structure of the cochlea. This makes it impossible to draw etiopathological conclusions. Recent pharmacokinetic studies have rejected the 'accumulation theory' of AGs in perilymph, while also in endolymph no accumulation can be found. Only a few data are available on inner ear tissue levels. Among the different pharmacodynamic hypotheses on the action of AGs, binding of the drug to acidic glycosaminoglycans in the stria vascularis, and interference by the drug with phosphoinositide metabolism in the hair cells seem to be of major importance.
Insights
Aminoglycoside antibiotics (AG) can cause ototoxicity, affecting hearing and balance. While incidence is estimated at 7.5%, risk factors remain unclear, and new research challenges accumulation theories.
Area of Science:
- Pharmacology
- Ototoxicology
- Internal Medicine
Background:
- Aminoglycoside antibiotics (AG) are crucial for treating bacterial infections.
- Otoxicity, a significant side effect of AGs, impacts both auditory (cochlear) and vestibular functions.
- Existing literature presents numerous controversies regarding AG-induced ototoxicity.
Purpose of the Study:
- To review and synthesize current literature on aminoglycoside-induced ototoxicity.
- To address controversies surrounding the incidence, risk factors, pathology, pharmacokinetics, and pharmacodynamics of AG ototoxicity.
- To explore potential mechanisms underlying AG ototoxicity.
Main Methods:
- Comprehensive literature review of studies on aminoglycoside ototoxicity.
- Analysis of epidemiological data for incidence estimation.
- Examination of pathological, pharmacokinetic, and pharmacodynamic studies.
- Evaluation of proposed risk factors and etiological hypotheses.
Main Results:
- Estimated incidence of cochlear and vestibulotoxic side-effects is 7.5% for each.
- Netilmicin shows a potentially lower ototoxic profile.
- Key risk factors like age, therapy duration, and organ dysfunction are likely important but not definitively established.
- Pathological changes in the cochlea are degenerative and unspecific.
- Pharmacokinetic studies refute AG accumulation in perilymph and endolymph.
- Key pharmacodynamic hypotheses involve drug binding to glycosaminoglycans and interference with phosphoinositide metabolism in hair cells.
Conclusions:
- Aminoglycoside ototoxicity remains a complex issue with unresolved controversies.
- While incidence is estimated, definitive risk factors and etiological pathways require further investigation.
- Current evidence challenges AG accumulation in inner ear fluids, shifting focus to cellular mechanisms.