title: The effects of exposure time, drug concentration, and temperature on the activity of ethambutol versus Mycobacterium tuberculosis.
abstract: In a series of dynamic in vitro studies designed to assess the activity of ethambutol (EMB) against Mycobacterium tuberculosis, we made the following observations. Ethambutol showed bactericidal action with 10 micrograms/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 degrees C and less at low temperatures. Ethambutol showed little activity against cultures growing at 8 degrees C continuously that were incubated for only 1 h at 37 degrees C. Against cultures growing at 8 degrees C that were brought to 37 degrees 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.
authors.affiliation: National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
authors.forename: P R
authors.initials: PR
authors.lastname: Gangadharam
authors.forename: P F
authors.initials: PF
authors.lastname: Pratt
authors.forename: V K
authors.initials: VK
authors.lastname: Perumal
authors.forename: M D
authors.initials: MD
authors.lastname: Iseman
mesh_terms: D004977:Ethambutol / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013696:Temperature; D013997:Time Factors
chemical_list: D004977:Ethambutol