[HTML][HTML] d-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models

DJ Fox, MD Cooper, CA Speil, MH Roberts… - Journal of Cystic …, 2016 - Elsevier
DJ Fox, MD Cooper, CA Speil, MH Roberts, SC Yanik, RP Meech, TL Hargrove, SJ Verhulst…
Journal of Cystic Fibrosis, 2016Elsevier
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 …
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 20 kHz in the 420 mg/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.
Elsevier