Ototoxicity aminoglycosides

Hutchin T, Cortopassi G. Proposed molecular and cellular mechanism for aminoglycoside ototoxicity. Antimicrob Agents Chemother 1994 38 2517-2520. 

Differences between different aminoglycosides Ototoxicity due to amikacin is primarily cochlear however, in comparisons with equipotent dosages, ototoxicity was of the same order as that caused by gentamicin (14-16). 

In a quantitative assessment of vestibular hair cells and Scarpa s ganglion cells in 17 temporal bones from 10 individuals with aminoglycoside ototoxicity, streptomycin caused a significant loss of both type I and type II hair cells in all five vestibular sense organs (19). The vestibular ototoxic effects of kanamycin appeared to be similar to those of streptomycin, whereas neomycin did not cause loss of vestibular hair cells. There was no significant loss of Scarpa s ganglion cells. 

Differences between sera from patients with resistance or susceptibility to aminoglycoside ototoxicity have been described in vitro (53). Sera from sensitive but not from resistant individuals metabolized aminoglycosides to cytotoxins, whereas no sera were cytotoxic when tested without the addition of aminoglycosides. This effect persisted for up to 1 year after aminoglycoside treatment. 

In an Italian family of whom five family members became deaf after aminoglycoside exposure, the nucleotide 961 thymidine deletion associated with a varying number of inserted cytosines in the mitochondrial 12S ribosomal RNA gene was identified as a second pathogenic mutation that could predispose to aminoglycoside ototoxicity (62). Molecular analysis excluded the A1555G mutation in this family. 

Matz GJ, Lerner SA. Prospective stndies of aminoglycoside ototoxicity in adults. In Lerner SA, Matz GJ, Hawkins JE, editors. Aminoglycoside Ototoxicity. Boston Little, Brown and Co, 1981 327. 

Tsuji K, Velazquez-Villasenor L, Rauch SD, Glynn RJ, Wall C 3rd, Merchant SN. Temporal bone studies of the human peripheral vestibular system. Aminoglycoside ototoxicity. Ann Otol Rhinol Laryngol Snppl 2000 181 20-5. 

Brummett RE, Fox KE. Studies of aminoglycoside ototoxicity in animal models. In Whelton A, Nen HC, editors. The Aminoglycosides. New York, Basel Marcel Dekker, 1982 419. 

Lima da Costa D, Erre JP, Pehourq F, Aran JM. Aminoglycoside ototoxicity and the medial efferent system II. Comparison of acnte effects of different antibiotics. Audiology 1998 37(3) 162-73. 

Kimnra N, Nishizaki K, Orita Y, Masnda Y. 4-methyl-catechol, a potent inducer of nerve growth factor synthesis, protects spiral ganglion neurons from aminoglycoside ototoxicity—preliminary report. Acta Otolaryngol Suppl 1999 540 12-15. 

Fischel-Ghodsian N, Prezant TR, Bn X, Oztas S. Mitochondrial ribosomal RNA gene mutation in a patient with sporadic aminoglycoside ototoxicity. Am J Otolaryngol 1993 14(6) 399 03. 

Schacht J. Aminoglycoside ototoxicity prevention in sight Otolaryngol Head Neck Surg 1998 118(5) 674-7. 

Casano RA, Johnson DF, Bykhovskaya Y, Torricelli F, Bigozzi M, Fischel-Ghodsian N. Inherited susceptibility to aminoglycoside ototoxicity genetic heterogeneity and clinical implications. Am J Otolaryngol 1999 20(3) 151-6. 

Guan MX, Fischel-Ghodsian N, Attardi G. A biochemical basis for the inherited susceptibility to aminoglycoside ototoxicity. Hum Mol Genet 2000 9(12) 1787-93. 

Conlon BJ, Smith DW. Topical aminoglycoside ototoxicity attempting to protect the cochlea. Acta Otolaryngol 2000 120(5) 596-9. 

Etacrynic acid potentiates aminoglycoside ototoxicity by facilitating the entry of the antibiotics from the systemic circulation into the endolymph (33). Animal evidence suggests that this effect may be potentiated by glutathione depletion (34). Conversely, neomycin can enhance the penetration of etacrynic acid into the inner ear (35). 

Hinojosa R, Nelson EG, Lerner SA, Redleaf MI, Schramm DR. Aminoglycoside ototoxicity a human temporal bone study. Laryngoscope 2001 lll(10) 1797-805. 

Histological examination of the temporal bones from two individuals with ototoxicity due to tobramycin showed reductions in the numbers of both ganglion cells and hair cells (21). Spiral ganglion cell loss was not necessarily subadjacent to areas of hair cell loss in cases of aminoglycoside ototoxicity. Instead, there may be a reduction in the number of ganglion cells in segments of the cochlea with normal-appearing hair cells. 

Sone M, Schachern PA, Paparella MM. Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity. Hear Res 1998 115(l-2) 217-23. 

Rizzi MD, Hirose K (2007) Aminoglycoside ototoxicity. Curr Opin Otolaryngol Head Neck Surg 15(5) 352-357... 

Fausti SA, Henry JA, Schaffer HI, Olson DJ, Frey RH, McDonald WJ (1992) High-frequency audiometric monitoring for early detection of aminoglycoside ototoxicity. J Infect Dis 165(6) 1026-1032... 

Alharazneh A, Luk L, Huth M, Monfared A, Steyger PS, Cheng AG, Ricci AJ (2011) Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity. PLoS One 6(7) e22347... 

Wu WJ, Sha SH, McLaren JD, Kawamoto K, Raphael Y, Schacht J (2001) Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat. Hear Res 158(1-2) 165-178... 

Matt T, Ng CL, Lang K, Sha SH, Akbergenov R, Shcherbakov D, Meyer M, Duscha S, Xie J, Dubbaka SR, Perez-Fernandez D, Vasella A, Ramakrishnan V, Schacht J, Bottger EC (2012) Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apra-mycin. Proc Natl Acad Sci U S A 109(27) 10984-10989... 

All aminoglycosides, including streptomycin, have the potential to produce irreversible vestibular and cochlear intoxication (16). Nonstreptomycin aminoglycosides are also renally toxic (16). The underlying causes of aminoglycoside ototoxicity are unresolved (reviewed in Ref 71). Multiple hypotheses exist to explain aminoglycoside ototoxicity, but none are com-... 

B. J. Conlon and D. W. Smith, Supplemental iron exacerbates aminoglycoside ototoxicity in... 

M. Yagi, E. Magal, Z. Sheng, K. A. Ang, and Y. Raphael, Hair cell protection from aminoglycoside ototoxicity by adenovirus-mediated overexpression of glial cell line-derived neurotrophic factor. Hum. Gene Ther., 10 (1999) 813-823. 

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