Ototoxicity of topical ticarcillin and clavulanic acid in the chinchilla
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T Jakob1, C G Wright, K Robinson
1Department of Otorhinolaryngology, University of Texas Southwestern Medical School, Dallas.
Background:
Currently available topical otic preparations contain a variety of antibiotics and other ingredients that are potentially damaging to the middle and inner ear. There is therefore a need to identify agents that are safe as well as effective for topical otologic use. In pursuit of that goal, we used an animal model to evaluate the ototoxic potential of the broad-spectrum, penicillin derivative ticarcillin--both alone and combined with clavulanic acid (a beta-lactamase inhibitor).
Methods:
Twenty chinchillas served as subjects. Ten of the animals were given a single middle ear application of ticarcillin; the remaining 10 animals received ticarcillin disodium plus clavulanate potassium (Timentin). Five animals from each of the two groups were killed after 1 week to assess short-term effects and the other five animals in each group were kept for 4 weeks before their temporal bones were removed for histologic study.
Results:
Significant toxic effects, involving both the middle and inner ear, were observed in all experimental groups. Alterations of the middle ear at 1 week included inflammation, hemorrhage, and effusions. Middle ear cholesteatomas were observed at 4 weeks. Inner ear changes seen at 1 and 4 weeks included hair cell loss, supporting cell degeneration, and strial damage.
Conclusion:
The study results indicate that ticarcillin should not be considered for further evaluation as a possible antibiotic for use in ototopical preparations.
Insights
Ticarcillin, a penicillin derivative, showed significant ototoxicity in animal models, causing damage to both middle and inner ears. These findings suggest ticarcillin is unsuitable for topical otologic preparations.
Area of Science:
- Ototoxicology
- Pharmacology
- Veterinary Medicine
Background:
- Existing topical otic preparations may harm the middle and inner ear.
- There is a need for safe and effective otologic agents.
- Ticarcillin, a penicillin derivative, was evaluated for ototoxicity.
Purpose of the Study:
- To assess the ototoxic potential of ticarcillin, alone and with clavulanic acid.
- To determine the safety of ticarcillin for topical otologic use.
Main Methods:
- Chinchillas were used as an animal model.
- Middle ear applications of ticarcillin or ticarcillin/clavulanate (Timentin) were administered.
- Histologic examination of temporal bones was performed at 1 and 4 weeks.
Main Results:
- All experimental groups exhibited significant middle and inner ear toxicity.
- Middle ear changes included inflammation, hemorrhage, effusions, and cholesteatomas.
- Inner ear damage involved hair cell loss, supporting cell degeneration, and strial damage.
Conclusions:
- Ticarcillin demonstrated considerable ototoxic effects in the animal model.
- Ticarcillin is not recommended for further investigation in topical otologic preparations.