Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use.

Scientific Reports
Masaaki IshikawaM Beatriz Durán-Alonso

Abstract

Spread of antimicrobial resistance and shortage of novel antibiotics have led to an urgent need for new antibacterials. Although aminoglycoside antibiotics (AGs) are very potent anti-infectives, their use is largely restricted due to serious side-effects, mainly nephrotoxicity and ototoxicity. We evaluated the ototoxicity of various AGs selected from a larger set of AGs on the basis of their strong antibacterial activities against multidrug-resistant clinical isolates of the ESKAPE panel: gentamicin, gentamicin C1a, apramycin, paromomycin and neomycin. Following local round window application, dose-dependent effects of AGs on outer hair cell survival and compound action potentials showed gentamicin C1a and apramycin as the least toxic. Strikingly, although no changes were observed in compound action potential thresholds and outer hair cell survival following treatment with low concentrations of neomycin, gentamicin and paromomycin, the number of inner hair cell synaptic ribbons and the compound action potential amplitudes were reduced. This indication of hidden hearing loss was not observed with gentamicin C1a or apramycin at such concentrations. These findings identify the inner hair cells as the most vulnerable element to AG ...Continue Reading

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Citations

Sep 16, 2020·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Diogo RaposoFilipe Freire
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Mar 5, 2021·American Journal of Audiology·Martha R WestmanM Patrick Feeney
Feb 24, 2021·Proceedings of the National Academy of Sciences of the United States of America·Javier Aguirre RiveraMagnus Johansson
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Jan 22, 2020·Journal of the American Chemical Society·Sivan Louzoun ZadaMicha Fridman
Aug 25, 2021·Nature Reviews. Chemistry·Marcus MiethkeRolf Müller

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