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Prevention and modulation of aminoglycoside ototoxicity (Review)

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Abstract
More than 60 years after their isolation and characterization, aminoglycoside (AG) antibiotics remain powerful agents in the treatment of severe gram-negative, enterococcal or mycobacterial infections. However, the clinical use of AGs is hampered by nephrotoxicity and ototoxicity, which often develop as a consequence of prolonged courses of therapy, or of administration of increased doses of these drugs. The discovery of non-ototoxic antibacterial agents, showing a wider spectrum of activity, has gradually decreased the use of AGs as first line antibiotics for many systemic infections. However, AGs are now undergoing an unexpected revival, being increasingly indicated for the treatment of severe emerging infections caused by organisms showing resistance to most first-line agents (e.g., multidrug-resistant tuberculosis, complicated nosocomially-acquired acute urinary tract infections). Increasing adoption of aminoglycosides poses again to scientists and physicians the problem of toxicity directed to the kidneys and to the inner ear. In particular, aminoglycoside-induced deafness can be profound and irreversible, especially in genetically predisposed patients. For this reason, an impressive amount of molecular strategies have been developed in the last decade to counteract the ototoxic effect of aminoglycosides. The present article overviews: i) the molecular mechanisms by which aminoglycosides exert their bactericidal activity, ii) the mechanisms whereby AGs exert their ototoxic activity in genetically-predisposed patients, iii) the drugs and compounds that have so far proven to prevent or modulate AG ototoxicity at the preclinical and/or clinical level, and iv) the dosage regimens that have so far been suggested to decrease the incidence of episodes of AG-induced ototoxicity.
Keywords
SENSORINEURAL DEAFNESS, COCHLEAR HAIR-CELLS, SYNDROMIC HEARING-LOSS, RIBOSOMAL-RNA GENE, FORMATION IN-VITRO, GENTAMICIN-INDUCED OTOTOXICITY, PROTECTS COCHLEAR, GUINEA-PIG, MITOCHONDRIAL DEAFNESS, A1555G MUTATION

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Citation

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MLA
Perletti, Gianpaolo et al. “Prevention and Modulation of Aminoglycoside Ototoxicity (Review).” MOLECULAR MEDICINE REPORTS 1.1 (2008): 3–13. Print.
APA
Perletti, Gianpaolo, Vral, A., Patrosso, M. C., Marras, E., Ceriani, I., Willems, P., Fasano, M., et al. (2008). Prevention and modulation of aminoglycoside ototoxicity (Review). MOLECULAR MEDICINE REPORTS, 1(1), 3–13.
Chicago author-date
Perletti, Gianpaolo, Anne Vral, Maria Cristina Patrosso, Emanuela Marras, Isabella Ceriani, Petra Willems, Mauro Fasano, and Vittorio Magri. 2008. “Prevention and Modulation of Aminoglycoside Ototoxicity (Review).” Molecular Medicine Reports 1 (1): 3–13.
Chicago author-date (all authors)
Perletti, Gianpaolo, Anne Vral, Maria Cristina Patrosso, Emanuela Marras, Isabella Ceriani, Petra Willems, Mauro Fasano, and Vittorio Magri. 2008. “Prevention and Modulation of Aminoglycoside Ototoxicity (Review).” Molecular Medicine Reports 1 (1): 3–13.
Vancouver
1.
Perletti G, Vral A, Patrosso MC, Marras E, Ceriani I, Willems P, et al. Prevention and modulation of aminoglycoside ototoxicity (Review). MOLECULAR MEDICINE REPORTS. 2008;1(1):3–13.
IEEE
[1]
G. Perletti et al., “Prevention and modulation of aminoglycoside ototoxicity (Review),” MOLECULAR MEDICINE REPORTS, vol. 1, no. 1, pp. 3–13, 2008.
@article{515940,
  abstract     = {{More than 60 years after their isolation and characterization, aminoglycoside (AG) antibiotics remain powerful agents in the treatment of severe gram-negative, enterococcal or mycobacterial infections. However, the clinical use of AGs is hampered by nephrotoxicity and ototoxicity, which often develop as a consequence of prolonged courses of therapy, or of administration of increased doses of these drugs. The discovery of non-ototoxic antibacterial agents, showing a wider spectrum of activity, has gradually decreased the use of AGs as first line antibiotics for many systemic infections. However, AGs are now undergoing an unexpected revival, being increasingly indicated for the treatment of severe emerging infections caused by organisms showing resistance to most first-line agents (e.g., multidrug-resistant tuberculosis, complicated nosocomially-acquired acute urinary tract infections). Increasing adoption of aminoglycosides poses again to scientists and physicians the problem of toxicity directed to the kidneys and to the inner ear. In particular, aminoglycoside-induced deafness can be profound and irreversible, especially in genetically predisposed patients. For this reason, an impressive amount of molecular strategies have been developed in the last decade to counteract the ototoxic effect of aminoglycosides. The present article overviews: i) the molecular mechanisms by which aminoglycosides exert their bactericidal activity, ii) the mechanisms whereby AGs exert their ototoxic activity in genetically-predisposed patients, iii) the drugs and compounds that have so far proven to prevent or modulate AG ototoxicity at the preclinical and/or clinical level, and iv) the dosage regimens that have so far been suggested to decrease the incidence of episodes of AG-induced ototoxicity.}},
  author       = {{Perletti, Gianpaolo and Vral, Anne and Patrosso, Maria Cristina and Marras, Emanuela and Ceriani, Isabella and Willems, Petra and Fasano, Mauro and Magri, Vittorio}},
  issn         = {{1791-2997}},
  journal      = {{MOLECULAR MEDICINE REPORTS}},
  keywords     = {{SENSORINEURAL DEAFNESS,COCHLEAR HAIR-CELLS,SYNDROMIC HEARING-LOSS,RIBOSOMAL-RNA GENE,FORMATION IN-VITRO,GENTAMICIN-INDUCED OTOTOXICITY,PROTECTS COCHLEAR,GUINEA-PIG,MITOCHONDRIAL DEAFNESS,A1555G MUTATION}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{3--13}},
  title        = {{Prevention and modulation of aminoglycoside ototoxicity (Review)}},
  volume       = {{1}},
  year         = {{2008}},
}

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