Ototoxic effect of daptomycin applied to the guinea pig middle ear.
CONCLUSIONS
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.
Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine , Sendai, Miyagi , Japan.
Hidetoshi
H
Oshima
Kazuhiro
K
Nomura
Muneharu
M
Yamazaki
Jun
J
Suzuki
Tetsuaki
T
Kawase
Toshimitsu
T
Kobayashi
Yukio
Y
Katori
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D017576:Daptomycin / Q000008:administration & dosage / Q000633:toxicity*; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000187:drug effects*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D034381:Hearing Loss / Q000139:chemically induced*; D008297:Male
D000900:Anti-Bacterial Agents; D017576:Daptomycin
Drug-resistant; eardrop; hearing; methicillin-resistant Staphylococcus aureus; topical; vancomycin