THE ROLE OF COPPER ON ETHAMBUTOLS ANTIMICROBIAL ACTION AND IMPLICATIONS FOR ETHAMBUTOL-INDUCED OPTIC NEUROPATHY

The principal side effect of the antimycobacterial agent ethambutol (E MB) is an optic neuropathy with clinical features very similar to a mi tochondrial hereditary optic neuropathy (Leber's). The mechanism of EM B-induced optic neuropathy may be EMB's chelation of copper, thereby p recluding normal cytochrome c oxidase activity and mitochondrial metab olism in the optic nerve. Before attempting to use therapeutic copper to replenish endogenous stoves in an attempt to preclude EMB-induced o ptic 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 radiometr ic broth macrodilution assay. Copper did not effect EMB's antimicrobia l 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 properti es. (C) 1998 Elsevier Science Inc.