The Effects of Exposure Time, Drug Concentration, and Temperature on the Activity of Ethambutol versusMycobacterium tuberculosis

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Abstract
In a series of dynamic in vitro studies designed to assess the activity of ethambutol (EMB) against M. tuberculosis, we made the following observations. Ethambutol showed bactericidal action with 10 .mu.g/ml concentration when in constant contact with M. tuberculosis. At a lower concentration, bactericidal action was evident up to 6 days; after that time, this effect was lost owing to the development of drug-resistant mutants. The bactericidal action of ethambutol in this model was similar to that of rifampin and isoniazid. Pulsed exposure for 96 h caused a four-log reduction in cfu counts, but the growth resumed rapidly. The bactericidal action of ethambutol was maximal at 37.degree.C and less at low temperatures. Ethambutol showed little activity against cultures growing at 8.degree.C continuously that were incubated for only 1 h at 37.degree.C. Against cultures growing at 8.degree.C that were brought to 37.degree.C for 6 h, its action was similar to that of rifampin. Ethambutol combined with other drugs showed bactericidal action, although the activity was less than that of the combination isoniazid-streptomycin.