Comparative vestibular toxicity study with 3-O-demethylfortimicin A disulfate and gentamicin sulfate in cats

3-O-demethylfortimicin A disulfate (ODMF), a novel aminocyclitol antibiotic, was administered subcutaneously for three months to groups of male and female cats at 15, 30 or 60 mg base/kg/day. Gentamicin sulfate (GS) at doses of 6 and 13 mg base/kg/day served as a reference compound. Signs of vestibular toxicity were considered to include persistent unsteady gait and stance, impaired righting reflex and abnormally diminished postrotatory vestibular nystagmus. Renal toxicities produced by ODMF and GS were also determined and compared. ODMF at 15 and 30 mg base/kg/day produced no signs of vestibular toxicity, while a dosage of 60 mg base/kg/day of ODMF produced vestibular toxicity in 7/10 cats. Three affected male cats died or were killed in moribund condition between study days 49 and 64. Vestibular toxicity was observed in 10/10 cats treated with GS at 13 mg base/kg/day and in 3/10 cats at 6 mg base/kg/day. All ten cats treated with GS at 13 mg base/kg/day died or were killed in moribund condition between study days 30 and 81. The deaths and moribundity in cats treated with ODMF or GS were attributed to renal toxicity. The vestibular toxicity and nephrotoxicity produced by ODMF and GS were more severe in male cats than in females. In conclusion, ODMF given at doses up to 60 mg base/kg/day for three months induced comparatively less vestibular toxicity and renal pathology than did GS at a dose of 13 mg base/kg/day.