Ototoxicity of vancomycin: an experimental study in guinea pigs.
Vancomycin (V)-a polypeptide antibiotic-is the drug of choice in severe infections with multiresistant staphylococcus spp. Due to the multimorbidity of the patients receiving V, the interactions with known ototoxic agents and the lack of an audiometric documentation, earlier clinical reports of V-associated hearing loss must be carefully interpreted. To elucidate this topic, a controlled animal study considering nonspecific effects was performed. 40 albino guinea pigs with positive Preyer's reflex and normal hearing were used. The hearing function was controlled by means of brainstem auditory evoked potentials before and after intraperitoneal administration of V (75, 150, 300 mg/kg b.w. for 11-17 days), gentamicin (60 mg/kg b.w. for 26 days), neomycin (100 mg/kg b.w. for 17 days) and sodium chloride solution. The cochleas were dissected for hair cell counting by the surface preparation technique. Additionally, the serum concentrations of V were measured. As a result there was no significant difference in hearing loss between the controls and the animals treated with 75 and 150 mg V; toxic doses of 300 mg V led to a certain threshold elevation after click stimuli, but not after trapezoid stimuli of 1, 4 and 8 kHz. On the other hand, the aminoglycosides as a positive control caused an obvious hearing loss after click and trapezoid stimuli, which was correlated to the amount of outer hair cell loss. Renal damage could be excluded by histological examination of the kidneys and estimation of creatinine in serum. Therefore, treatment with moderate doses of V comparable to clinical conditions does not exhibit a specific ototoxicity as compared to the aminoglycosides.(ABSTRACT TRUNCATED AT 250 WORDS)
Lutz
H
H
Department of Otolaryngology, University of Heidelberg, FRG.
Lenarz
T
T
Weidauer
H
H
Federspil
P
P
Hoth
S
S
D000818:Animals; D001300:Audiometry, Evoked Response; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005839:Gentamicins / Q000009:adverse effects / Q000494:pharmacology; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000473:pathology; D006311:Hearing Disorders / Q000139:chemically induced*; D009355:Neomycin / Q000009:adverse effects / Q000494:pharmacology; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D011930:Reaction Time / Q000187:drug effects; D014640:Vancomycin / Q000009:adverse effects / Q000494:pharmacology*
D005839:Gentamicins; D014640:Vancomycin; D009355:Neomycin