Comparative evaluation of the antibacterial activity and toxicity of a large panel of aminoglycoside antibiotics
10 affiliations
- 1Unit of Excellence, Institute of Biomedicine and Molecular Genetics (IBGM), University of Valladolid-CSIC
- 2Acies Bio, d.o.o
- 3Service of Microbiology, University Hospital Marqués de Valdecilla
- 4Instituto de Investigacion Valdecilla (IDIVAL)
- 5Department of Analytical Chemistry, National Institute of Chemistry
- 6Unit of Microbiology, University Hospital Reina Sofía
- 7Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)
- 8Department of Microbiology, University of Córdoba
- 9Biotechnical Faculty, University of Ljubljana
- 10Department of Biochemistry and Molecular Biology and Physiology, Faculty of Medicine, University of Valladolid
Abstract
Background: There is a critical need for the development of novel antibiotics due to widespread occurrence of multidrug resistance. Despite their adverse effects, namely, nephrotoxicity and ototoxicity, the emergence of multi-drug resistant bacteria that are resistant to potent antibiotics such as the fluoroquinolones and the ß-lactams has highlighted the prominent role of aminoglycoside antibiotics (AGs).
Methods: We carried out a comprehensive comparative characterization of the antibacterial efficacy of a whole series of AGs and AG congeners against a large panel of 61 well characterized ESKAPE clinical isolates, and investigated their ototoxic and nephrotoxic potential, using the OC-k3 and HEI-OC1 otic cell lines and the kidney LLC-PK1 cell line, respectively, all under a common set of experimental conditions; additionally, a selection of these AGs was tested on murine cochlear explants; this information is not available in the literature.
Results: Out of 26 AGs tested, eight commercial AGs and four AG congeners demonstrated strong antibacterial activity against multi-drug resistant pathogens. Eight commercial AGs (amikacin, apramycin, gentamicin, isepamicin, neomycin, paromomycin, sisomicin and tobramycin) and four AG congeners (gentamicin C1a, C2, C2a and neomycin B) demonstrated strong antibacterial activity. Amikacin and isepamicin did not exert toxicity on murine cochlear explants. In addition, amikacin was the only one that did not exert significant nephrotoxicity on the LLC-PK1 cell line. Work on cochlear explants identified neomycin B and gentamicin C1a congeners as less ototoxic than their corresponding AG mixtures, although the congeners were more nephrotoxic. Importantly, we have for the first time directly compared the antibacterial activity and toxicity of seven of the most common gentamicin congeners. We identified gentamicin congeners B1 and X2 as highly toxic, while exhibiting very low antibacterial activity.
Conclusion: We have demonstrated the utility of natural and semi-synthetic AGs against a large panel of multidrug-resistant clinical isolates present in our hospitals. We carried out a comparative assessment of the nephro- and ototoxicity of all these AGs and our data particularly highlighted a very high toxicity of the gentamicin congeners B1 and X2; these congeners may be present in small amounts in commercial gentamicin mixtures and their high toxicity, generally overlooked, could have serious negative implications when gentamicin formulations are applied in the clinic. Nonetheless, it must be taken into account that these studies were conducted on cell lines and, although the concentrations of AGs that are recorded in patients’ plasma are variable, -depending on factors such as dosing regimens and the infectious agent-, the AG concentrations we applied to the cultures are well above these concentrations; confirmation of these results in in vivo models will thus be required.
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BibTeX
@article{garciamateo2026comparative,
title = {{Comparative evaluation of the antibacterial activity and toxicity of a large panel of aminoglycoside antibiotics}},
author = {Nadia García-Mateo and Iris López-Hernández and Alen Čusak and Marta Fernández-Martínez and Martin Šala and Thomas Schimmang and Gregor Kosec and Štefan Fujs and Luis Martínez-Martínez and Hrvoje Petković and M. Beatriz Durán-Alonso},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1930759},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1930759/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparative evaluation of the antibacterial activity and toxicity of a large panel of aminoglycoside antibiotics
AU - Nadia García-Mateo
AU - Iris López-Hernández
AU - Alen Čusak
AU - Marta Fernández-Martínez
AU - Martin Šala
AU - Thomas Schimmang
AU - Gregor Kosec
AU - Štefan Fujs
AU - Luis Martínez-Martínez
AU - Hrvoje Petković
AU - M. Beatriz Durán-Alonso
PY - 2026
DA - 2026/10/15
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1930759
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1930759/full
AB - Background: There is a critical need for the development of novel antibiotics due to widespread occurrence of multidrug resistance. Despite their adverse effects, namely, nephrotoxicity and ototoxicity, the emergence of multi-drug resistant bacteria that are resistant to potent antibiotics such as the fluoroquinolones and the ß-lactams has highlighted the prominent role of aminoglycoside antibiotics (AGs). Methods: We carried out a comprehensive comparative characterization of the antibacterial efficacy of a whole series of AGs and AG congeners against a large panel of 61 well characterized ESKAPE clinical isolates, and investigated their ototoxic and nephrotoxic potential, using the OC-k3 and HEI-OC1 otic cell lines and the kidney LLC-PK1 cell line, respectively, all under a common set of experimental conditions; additionally, a selection of these AGs was tested on murine cochlear explants; this information is not available in the literature. Results: Out of 26 AGs tested, eight commercial AGs and four AG congeners demonstrated strong antibacterial activity against multi-drug resistant pathogens. Eight commercial AGs (amikacin, apramycin, gentamicin, isepamicin, neomycin, paromomycin, sisomicin and tobramycin) and four AG congeners (gentamicin C1a, C2, C2a and neomycin B) demonstrated strong antibacterial activity. Amikacin and isepamicin did not exert toxicity on murine cochlear explants. In addition, amikacin was the only one that did not exert significant nephrotoxicity on the LLC-PK1 cell line. Work on cochlear explants identified neomycin B and gentamicin C1a congeners as less ototoxic than their corresponding AG mixtures, although the congeners were more nephrotoxic. Importantly, we have for the first time directly compared the antibacterial activity and toxicity of seven of the most common gentamicin congeners. We identified gentamicin congeners B1 and X2 as highly toxic, while exhibiting very low antibacterial activity. Conclusion: We have demonstrated the utility of natural and semi-synthetic AGs against a large panel of multidrug-resistant clinical isolates present in our hospitals. We carried out a comparative assessment of the nephro- and ototoxicity of all these AGs and our data particularly highlighted a very high toxicity of the gentamicin congeners B1 and X2; these congeners may be present in small amounts in commercial gentamicin mixtures and their high toxicity, generally overlooked, could have serious negative implications when gentamicin formulations are applied in the clinic. Nonetheless, it must be taken into account that these studies were conducted on cell lines and, although the concentrations of AGs that are recorded in patients’ plasma are variable, -depending on factors such as dosing regimens and the infectious agent-, the AG concentrations we applied to the cultures are well above these concentrations; confirmation of these results in in vivo models will thus be required.
SN - 1663-9812
ER -