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Updated: Apr 7, 2026

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
d-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models
Daniel J Fox1, Morris D Cooper2, Cristian A Speil3
1Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA; Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA; Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
Background:
Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested d-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference.
Methods:
Auditory brainstem responses (ABRs) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of d-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic Escherichia coli murine survival and intraperitoneal lavage bacterial counts.
Results:
d-Methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20kHz in the 420mg/kg/day group. In vitro studies did not detect d-methionine-induced antimicrobial interference. In vivo studies did not detect d-methionine-induced interference in normal or neutropenic mice.
Conclusions:
d-Methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest d-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients.
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