Inner ear concentrations and ototoxicity of different antibiotics in local and systemic application

TLDR

Ototoxicity of aminoglycoside antibiotics is linked to their specific accumulation in the inner ear’s endolymph and perilymph. The study aimed to determine whether inner‑ear concentrations of aminoglycosides correlate with hair‑cell damage. Researchers compared isomolar doses of aminoglycosides, measured their inner‑ear levels, and assessed sensory‑cell loss using surface‑preparation microscopy. Higher inner‑ear concentrations of aminoglycosides produced greater hair‑cell damage, while polymyxins and tetracyclines were ototoxic only when applied topically, chloramphenicol and erythromycin also caused topical damage, and penicillin showed no inner‑ear damage regardless of route.

Abstract

The cause of the specific ototoxicity of antibiotics of the aminoglycosid group, like streptomycin, kanamycin, neomycin, gentamicin, may, as we could observe, be looked for in the specific accumulation of these substances both in the endolymph and perilymph of the internal ear. The toxicity may be explained by the high concentration of these antibiotics in the lymphatic fluid and by the fact, that they are retained there for a long time.In a comparative study with isomolar doses of the toxic aminoglycosid antibiotics, both the extent of sensory (hair) cell damages using the surface preparation technique were evaluated and the antibiotic level was measured. It could be shown that the more toxic the substance, the higher was the concentration in the internal ear. This specific accumulation and toxicity, typical for each substance, could be found both in systemic intramuscular and direct (topical) application to the cochlea.On the other hand, when other antibiotics were applied, either in a systemic or topical mode, basic differences became apparent. Thus, the neurotoxic polymyxins and tetracyclines, when applied intramuscularly, did not cause any damages to hearing because of their inability to penetrate the internal ear, that is, through the blood-lymph barrier. Topically applied, polymyxin causes severe sensory cell damages and, to a smaller extent, tetracycline, too. Furthermore, chloramphenicol topically applied, will cause sensory cell damages. The pronounced damages caused by the topical application of erythromycin, were also surprising. Only penicillin, independent of its mode of application, showed no internal ear damages, the result being identical with the control tests.