Effects of antibiotic-diuretic interactions in the guinea pig model of ototoxicity

Abstract

The guinea pig model has been useful for estimating quantitatively the ototoxic effects of many different drugs. Our model utilizes measures of the Preyer pinna reflex, the alternating current cochlear potential and sensory hair-cell morphology to access drug effects. The principle pathophysiologic lesion of aminoglycoside-induced permanent ototoxicity appears to be sensory hair-cell loss in the organ of Corti. Aminoglycoside antibiotics were found to interact with loop-inhibiting diuretics, and the augmented ototoxic effects were attributed to hair-cell destruction. The interaction is specific for loop-inhibiting diuretics but not for the aminoglycosides since nonaminoglycoside antibiotics, such as viomycin and polymixin B, interacted similarly. Noninteractive antibiotics include amphotericin B and vancomycin. The absence of ototoxic effects with vancomycin is of interest in view of its broadening clinical utility.