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Ototoxic effect of daptomycin applied to the guinea pig middle ear
Hidetoshi Oshima1, Kazuhiro Nomura, Muneharu Yamazaki
1Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine , Sendai, Miyagi , Japan.
Conclusion:
Daptomycin applied topically at a concentration of 50 mg/ml caused mild but statistically significant hearing impairment. Outer hair cells were not damaged by daptomycin. Great care must be taken when there is a chance that daptomycin can reach the middle ear.
Objective:
Ototopic antibiotic eardrops are frequently used to treat external and middle ear infections. Daptomycin is a new anti-methicillin-resistant Staphylococccus aureus (MRSA) drug with unknown ototoxicity. The current study examined the ototoxic effect of daptomycin in topical applications to guinea pig ears.
Methods:
Twenty-three male Hartley guinea pigs (weight, 250-640 g) were divided into three groups receiving daptomycin (50 mg/ml), gentamicin (50 mg/ml, positive control), or saline solution (negative control). After insertion of a pressure-equalizing tube, pretreatment auditory brainstem responses (ABRs) were obtained. Topical solutions of 0.1 ml were applied through the tube into the middle ear twice a day for 7 days. Post-treatment ABRs were obtained 7 days after the last treatment. Hair cell loss was investigated with whole-mount cochlear surface preparations.
Results:
The saline-treated (negative control) group showed no deterioration of ABR threshold. The daptomycin-treated group showed mild deterioration and the gentamicin-treated group showed severe deterioration in ABR threshold. Hair cells were preserved in the daptomycin- and saline-treated groups but severely damaged in the gentamicin group.
Insights
Topical daptomycin (50 mg/ml) caused mild hearing impairment in guinea pigs, with no damage to outer hair cells. Caution is advised if daptomycin reaches the middle ear.
Area of Science:
- Ototoxicity studies
- Pharmacology
- Auditory science
Background:
- Topical antibiotic eardrops are common for ear infections.
- Daptomycin is a novel antibiotic for MRSA with uncharacterized ototoxicity.
- This study investigates daptomycin's ototoxic potential.
Purpose of the Study:
- To evaluate the ototoxic effects of topical daptomycin.
- To compare daptomycin's ototoxicity to gentamicin and saline controls.
- To assess effects on auditory brainstem responses and cochlear hair cells.
Main Methods:
- Guinea pigs received topical daptomycin, gentamicin, or saline via pressure-equalizing tubes.
- Auditory brainstem responses (ABRs) were measured pre- and post-treatment.
- Cochlear hair cell integrity was examined post-treatment.
Main Results:
- Daptomycin caused mild ABR threshold deterioration; gentamicin caused severe deterioration.
- Hair cells remained intact in daptomycin and saline groups.
- Gentamicin severely damaged cochlear hair cells.
Conclusions:
- Topical daptomycin at 50 mg/ml induces mild, statistically significant hearing impairment.
- Outer hair cells are not affected by daptomycin.
- Care is necessary to prevent daptomycin exposure to the middle ear.
