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Effect of topical fosfomycin on polymyxin B ototoxicity
J L Leach1, C G Wright, L B Edwards
1Department of Otorhinolaryngology, University of Texas Southwestern Medical Center, Dallas.
Abstract:
Fosfomycin is an antibiotic that has been found to reduce the ototoxicity of aminoglycoside antibiotics and cisplatin when systemically coadministered. Polymyxin B, an antibiotic frequently used in ototopical preparations, has been shown to be ototoxic in experimental studies. To investigate the effect of fosfomycin on polymyxin B ototoxicity, topical administration of the two agents into the middle ear cavity was performed. Two groups of chinchillas were used. One group received applications of polymyxin B alone, and the second group received polymyxin B combined with fosfomycin. It was found that application of polymyxin B produces severe damage to the cochlea. However, when polymyxin B was given in combination with fosfomycin, cochlear damage was dramatically reduced. It is likely that in clinical use, a combination of polymyxin B and fosfomycin would demonstrate reduced risk of ototoxicity.
Insights
Fosfomycin significantly reduces the ototoxicity of Polymyxin B when applied topically to the middle ear. This combination therapy shows promise for minimizing hearing damage associated with Polymyxin B use.
Area of Science:
- Otolaryngology
- Pharmacology
- Ototoxicity research
Background:
- Fosfomycin (antibiotic) mitigates ototoxicity from aminoglycosides and cisplatin.
- Polymyxin B (antibiotic) is ototoxic, despite common topical use.
Purpose of the Study:
- To evaluate the protective effect of fosfomycin against Polymyxin B-induced ototoxicity.
- Investigate topical coadministration of fosfomycin and Polymyxin B in the middle ear.
Main Methods:
- Chinchilla model utilized for topical middle ear administration.
- Two groups: Polymyxin B alone vs. Polymyxin B with fosfomycin.
- Cochlear damage assessed post-treatment.
Main Results:
- Polymyxin B alone caused severe cochlear damage.
- Combination with fosfomycin dramatically reduced Polymyxin B-induced cochlear damage.
Conclusions:
- Fosfomycin effectively protects against Polymyxin B ototoxicity.
- Topical coadministration of Polymyxin B and fosfomycin may reduce clinical ototoxicity risk.