title: The role of copper on ethambutol's antimicrobial action and implications for ethambutol-induced optic neuropathy.
abstract: The principal side effect of the antimycobacterial agent ethambutol (EMB) is an optic neuropathy with clinical features very similar to a mitochondrial hereditary optic neuropathy (Leber's). The mechanism of EMB-induced optic neuropathy may be EMB's chelation of copper, thereby precluding normal cytochrome c oxidase activity and mitochondrial metabolism in the optic nerve. Before attempting to use therapeutic copper to replenish endogenous stores in an attempt to preclude EMB-induced optic neuropathy, we wished to determine whether EMB is still effective against mycobacteria in the presence of copper. EMB and copper, alone and in combination, were tested against six strains of Mycobacterium tuberculosis and five strains of Mycobacterium avium using a radiometric broth macrodilution assay. Copper did not effect EMB's antimicrobial actions against either species of mycobacteria. This in vitro study suggests that if copper were given to patients to prevent EMB-induced optic neuropathy, it would not compromise EMB's bacteriostatic properties.
authors.affiliation: Department of Ophthalmology and Neurosurgery, Doheny Eye Institute, University of Southern California School of Medicine, Los Angeles 90033, USA.
authors.forename: S F
authors.initials: SF
authors.lastname: Kozak
authors.forename: C B
authors.initials: CB
authors.lastname: Inderlied
authors.forename: H Y
authors.initials: HY
authors.lastname: Hsu
authors.forename: K B
authors.initials: KB
authors.lastname: Heller
authors.forename: A A
authors.initials: AA
authors.lastname: Sadun
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000075202:Contraindications; D003300:Copper / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004977:Ethambutol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009162:Mycobacterium avium / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D018917:Optic Neuropathy, Ischemic / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000995:Antitubercular Agents; D003300:Copper; D004977:Ethambutol