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

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. doi: 10.1038/s41598-019-38634-3.
Masaaki Ishikawa 1 2,  Nadia García-Mateo 3,  Alen Čusak 4,  Iris López-Hernández 3,  Marta Fernández-Martínez 5 6,  Marcus Müller 7,  Lukas Rüttiger 1,  Wibke Singer 1,  Hubert Löwenheim 7,  Gregor Kosec 4,  Štefan Fujs 4,  Luis Martínez-Martínez 8 9 10,  Thomas Schimmang 3,  Hrvoje Petković 4 11,  Marlies Knipper 12,  M Beatriz Durán-Alonso 13
Affiliations

Affiliations

  • 1 Molecular Physiology of Hearing, Department of Otolaryngology, Tübingen Hearing Research Centre (THRC), University of Tübingen, Tübingen, Germany.
  • 2 Graduate School of Medicine, Department of Otolaryngology, Kyoto University, Kyoto, Japan.
  • 3 Institute of Biology and Molecular Genetics (IBGM), University of Valladolid-CSIC, Valladolid, Spain.
  • 4 Acies Bio d.o.o., Ljubljana, Slovenia.
  • 5 University Hospital Marqués de Valdecilla IDIVAL, Santander, Spain.
  • 6 Universidad de Cantabria, Santander, Spain.
  • 7 Department of Otorhinolaryngology, Tübingen Hearing Research Centre (THRC), Regenerative Medicine, University of Tübingen, Tübingen, Germany.
  • 8 Unit of Microbiology, University Hospital Reina Sofía, Córdoba, Spain.
  • 9 Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
  • 10 Department of Microbiology, University of Córdoba, Córdoba, Spain.
  • 11 Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
  • 12 Molecular Physiology of Hearing, Department of Otolaryngology, Tübingen Hearing Research Centre (THRC), University of Tübingen, Tübingen, Germany. marlies.knipper@uni-tuebingen.de.
  • 13 Institute of Biology and Molecular Genetics (IBGM), University of Valladolid-CSIC, Valladolid, Spain. mbduran@ibgm.uva.es.
PMID: 30787404 DOI: 10.1038/s41598-019-38634-3
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 treatment, indicating that gentamicin C1a and apramycin are promising bases for the development of clinically useful Antibiotics.

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