Cargando…
Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use
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 ev...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382871/ https://www.ncbi.nlm.nih.gov/pubmed/30787404 http://dx.doi.org/10.1038/s41598-019-38634-3 |
_version_ | 1783396737903230976 |
---|---|
author | Ishikawa, Masaaki García-Mateo, Nadia Čusak, Alen López-Hernández, Iris Fernández-Martínez, Marta Müller, Marcus Rüttiger, Lukas Singer, Wibke Löwenheim, Hubert Kosec, Gregor Fujs, Štefan Martínez-Martínez, Luis Schimmang, Thomas Petković, Hrvoje Knipper, Marlies Durán-Alonso, M. Beatriz |
author_facet | Ishikawa, Masaaki García-Mateo, Nadia Čusak, Alen López-Hernández, Iris Fernández-Martínez, Marta Müller, Marcus Rüttiger, Lukas Singer, Wibke Löwenheim, Hubert Kosec, Gregor Fujs, Štefan Martínez-Martínez, Luis Schimmang, Thomas Petković, Hrvoje Knipper, Marlies Durán-Alonso, M. Beatriz |
author_sort | Ishikawa, Masaaki |
collection | PubMed |
description | 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 treatment, indicating that gentamicin C1a and apramycin are promising bases for the development of clinically useful antibiotics. |
format | Online Article Text |
id | pubmed-6382871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63828712019-02-25 Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use Ishikawa, Masaaki García-Mateo, Nadia Čusak, Alen López-Hernández, Iris Fernández-Martínez, Marta Müller, Marcus Rüttiger, Lukas Singer, Wibke Löwenheim, Hubert Kosec, Gregor Fujs, Štefan Martínez-Martínez, Luis Schimmang, Thomas Petković, Hrvoje Knipper, Marlies Durán-Alonso, M. Beatriz Sci Rep Article 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 treatment, indicating that gentamicin C1a and apramycin are promising bases for the development of clinically useful antibiotics. Nature Publishing Group UK 2019-02-20 /pmc/articles/PMC6382871/ /pubmed/30787404 http://dx.doi.org/10.1038/s41598-019-38634-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ishikawa, Masaaki García-Mateo, Nadia Čusak, Alen López-Hernández, Iris Fernández-Martínez, Marta Müller, Marcus Rüttiger, Lukas Singer, Wibke Löwenheim, Hubert Kosec, Gregor Fujs, Štefan Martínez-Martínez, Luis Schimmang, Thomas Petković, Hrvoje Knipper, Marlies Durán-Alonso, M. Beatriz Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use |
title | Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use |
title_full | Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use |
title_fullStr | Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use |
title_full_unstemmed | Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use |
title_short | Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use |
title_sort | lower ototoxicity and absence of hidden hearing loss point to gentamicin c1a and apramycin as promising antibiotics for clinical use |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382871/ https://www.ncbi.nlm.nih.gov/pubmed/30787404 http://dx.doi.org/10.1038/s41598-019-38634-3 |
work_keys_str_mv | AT ishikawamasaaki lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT garciamateonadia lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT cusakalen lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT lopezhernandeziris lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT fernandezmartinezmarta lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT mullermarcus lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT ruttigerlukas lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT singerwibke lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT lowenheimhubert lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT kosecgregor lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT fujsstefan lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT martinezmartinezluis lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT schimmangthomas lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT petkovichrvoje lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT knippermarlies lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse AT duranalonsombeatriz lowerototoxicityandabsenceofhiddenhearinglosspointtogentamicinc1aandapramycinaspromisingantibioticsforclinicaluse |