RT Journal Article
T1 Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use.
A1 Ishikawa, Masaaki
A1 Garcia-Mateo, Nadia
A1 Čusak, Alen
A1 Lopez-Hernandez, Iris
A1 Fernandez-Martinez, Marta
A1 Müller, Marcus
A1 Rüttiger, Lukas
A1 Singer, Wibke
A1 Löwenheim, Hubert
A1 Kosec, Gregor
A1 Fujs, Štefan
A1 Martinez-Martinez, Luis
A1 Schimmang, Thomas
A1 Petković, Hrvoje
A1 Knipper, Marlies
A1 Duran-Alonso, M Beatriz
K1 Hearing Loss
K1 Nebramycin
K1 Neomycin
K1 Ototoxicity
K1 Protein Synthesis Inhibitors
K1 Round Window, Ear
AB 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.
PB Nature Publishing Group
YR 2018
FD 2018-11-29
LK http://hdl.handle.net/10668/13601
UL http://hdl.handle.net/10668/13601
LA en
NO Ishikawa M, García-Mateo N, Čusak A, López-Hernández I, Fernández-Martínez M, Müller M, Rüttiger L, et al. Lower ototoxicity and absence of hidden hearing loss point to gentamicin C1a and apramycin as promising antibiotics for clinical use. Sci Rep. 2019 Feb 20;9(1):2410
NO Tis study was supported by TRIH grants/Action on Hearing Loss (Grant No. Project No. T3_Petkovic), the Deutsche Forschungsgemeinschaf SPP 1608 RU 316/12-1; SPP1608 KN 316/12-1. Te authors thank Prof. Federico Kalinec for kindly providing the otic cell lines, and Prof. Jochen Schacht for advice on the organotypic explant work. We also thank Sergio Díez-Hermano for help with the statistical analyses, as well as Cristina Sánchez and Yolanda Noriega for their assistance in confocal microscopy. Dr Marta Fernández-Martínez and Dr Luis Martínez-Martínez are supported by Plan Nacional de I + D + i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0007 and RD16/0016/0008, respectively), and co-fnanced by the European Development Regional Fund “A way to achieve Europe”, Operative Program Intelligent Growth 2014–2020
DS RISalud
RD Apr 14, 2025