title: Aminoglycosides: therapeutics, ototoxicity and hypersensitivity of mitochondrial genetic origin.
abstract: Aminoglycosides such as streptomycin or gentamycin are employed to treat stubborn infections. In México, tuberculosis patients are successfully treated with 1 g/day for over 6 months. Ototoxicity is often seen as a consequence of prolonged treatment with aminoglycosides. In young people STP damages the vestibule of the ear; in elder patients it diminishes hearing and balance. These effects are due to streptidine, a metabolite of STP produced in elder patients and detected in blood by liquid chromatography. On occasion, sudden deafness is established after only a short treatment period as the result of the presence of a single nucleotide mutation in the mitochondrial 12S rRNA gene. In patients with this polymorphism, aminoglycosides produce a stereotypic conformation similar to the bacterial 16S rRNA thus inhibiting the synthesis of proteins. Many aminoglycoside-sensitive mutations have been described in several ethnic groups, causing sudden deafness. We started similar studies in Mexican individuals, treated or not with an aminoglycoside, to determine whether similar alterations could be detected. To date in over 60 individuals analyzed we found only one case of polymorphism in a streptomycin treated patient. We developed a simple method to identify such mitochondrial gene in a larger population to make recommendations to use an alternative treatment which do not cause ototoxicity in the mutation bearing patient.
authors.affiliation: Departamento Neuropatología Molecular, Instituto de Fisiologio Celular, UNAM. Email: gmeza@ifc.unam.mx.
authors.forename: N M
authors.initials: NM
authors.lastname: Torres-Ruíz
authors.forename: O
authors.initials: O
authors.lastname: Granados
authors.forename: G
authors.initials: G
authors.lastname: Meza
mesh_terms: D000328:Adult; D000617:Aminoglycosides / Q000009:adverse effects*; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000209:etiology*; D006309:Hearing / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009154:Mutation; D012335:RNA, Ribosomal / Q000235:genetics*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S