title: d-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department 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. Electronic address: dfox@siumed.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fox
authors.affiliation: Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Morris D
authors.initials: MD
authors.lastname: Cooper
authors.affiliation: Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Cristian A
authors.initials: CA
authors.lastname: Speil
authors.affiliation: Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Melissa H
authors.initials: MH
authors.lastname: Roberts
authors.affiliation: Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Yanik
authors.affiliation: Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Meech
authors.affiliation: Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Tim L
authors.initials: TL
authors.lastname: Hargrove
authors.affiliation: Statistics and Research Consulting, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Verhulst
authors.affiliation: Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Leonard P
authors.initials: LP
authors.lastname: Rybak
authors.affiliation: Department of Surgery, Southern Illinois University School of Medicine, Springfield, IL, USA; Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA.
authors.forename: Kathleen C M
authors.initials: KC
authors.lastname: Campbell
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects; D003550:Cystic Fibrosis / Q000188:drug therapy*; D016903:Drug Monitoring / Q000379:methods; D004427:Ear Diseases / Q000139:chemically induced / Q000517:prevention & control; D004926:Escherichia coli / Q000187:drug effects; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000473:pathology*; D008715:Methionine / Q000494:pharmacology*; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology; D014031:Tobramycin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000890:Anti-Infective Agents; D020011:Protective Agents; D008715:Methionine; D014031:Tobramycin
keywords: Aminoglycoside; Antimicrobial interference; Otoprotection; Ototoxicity; d-Methionine