Protective effect of fosfomycin against aminoglycoside ototoxicity.
The protective effect of fosfomycin against aminoglycoside (dibekacin)-induced ototoxicity was studied in rats. Rats were injected with 100 or 50 mg/kg of dibekacin with or without 500 mg/kg of fosfomycin for 60 or 120 consecutive days. Inner ear damage appeared to be more reduced histopathologically in animals given both dibekacin and fosfomycin than in animals given dibekacin alone. Similarly, renal damage appeared to be reduced histopathologically and functionally by the combined administration of dibekacin and fosfomycin. The mechanism of reduced ototoxicity may be as follows: fosfomycin inhibits the accumulation of dibekacin in the kidney, and reduces its concentration in the kidney and serum. Consequently, the amounts of dibekacin reaching the inner ear are decreased, and ototoxicity is reduced.
D000118:Acetylglucosaminidase / Q000097:blood; D000617:Aminoglycosides / Q000009:adverse effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D003051:Cochlea / Q000187:drug effects; D003982:Dibekacin / Q000009:adverse effects / Q000097:blood; D005578:Fosfomycin / Q000097:blood / Q000627:therapeutic use*; D006198:Hair Cells, Auditory / Q000473:pathology; D007668:Kidney / Q000032:analysis / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007759:Labyrinth Diseases / Q000139:chemically induced* / Q000473:pathology; D010498:Perilymph / Q000032:analysis; D011507:Proteinuria; D051381:Rats
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D003982:Dibekacin; D000118:Acetylglucosaminidase