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PubMed1998

Evaluation of the ESP culture system II for testing susceptibilities of Mycobacterium tuberculosis isolates to four primary antituberculous drugs.

The reliability of the ESP Culture System II (herein referred to as ESP II) for testing susceptibilities of Mycobacterium tuberculosis isolates to isoniazid, rifampin, ethambutol, and streptomycin was evaluated by comparing results to those of the method of proportion (MOP), which was considered the reference method, for 20 clinical isolates and 30 challenge strains provided by the Centers for Disease Control and Prevention (CDC). Clinical isolates also were tested with the BACTEC TB 460 system; these results agreed with those obtained by the MOP for all isolates and all drugs, except the high concentration of isoniazid, for which agreement was 95%. After resolution of discrepancies, levels of agreement between ESP II and MOP for the clinical isolates were 95 and 100%, respectively, for the low and high concentrations of isoniazid, 100% for rifampin and ethambutol, and 95% for streptomycin. For the 30 challenge isolates, ESP II results for both concentrations of isoniazid agreed with the expected results in all cases, whereas agreement was 93% for both rifampin and streptomycin and 90% for ethambutol. All discrepancies with the CDC isolates were due to failure of ESP II to correctly classify resistant strains. By testing isolates yielding discrepant ethambutol and streptomycin results with a lower concentration of both drugs in the ESP II system, agreement increased to 93% for ethambutol and 100% for streptomycin. For the clinical isolates, the times to an ESP II result of susceptible (means +/- standard errors of the means) were 8.47 +/- 0.12 days (range, 7 to 10 days) and 8.73 +/- 0.29 days (range, 5 to 11 days) when the inoculum was prepared from a McFarland equivalent and from a seed bottle, respectively. The time to an ESP II result of resistant varied by drug and method of inoculum preparation, ranging from 5.50 +/- 0.22 days for ethambutol with the inoculum prepared from a McFarland standard to 8. 0 days for ethambutol with the inoculum prepared from a seed bottle. These data suggest that the ESP II system is a rapid and reliable method for testing susceptibilities of M. tuberculosis isolates to isoniazid and rifampin. Performance, however, may be suboptimal for ethambutol and streptomycin. Testing additional ethambutol-resistant and streptomycin-resistant strains with two concentrations of both drugs is necessary.

Antitubercular Agents↗
PubMed1991

Induced color blindness in goldfish: a behavioral and electrophysiological study.

To answer the question whether, like man, ethambutol treated fish would become color-blind, wavelength discrimination was measured behaviorally in goldfish, preceding, during and after ethambutol treatment. The results are that of the three high discrimination abilities at around 400, 500 and 600 nm, ethambutol affected the latter one. Red-green discrimination is lost reversibly leaving the discriminations in the blue-green and violet range unaffected. This red-green discrimination deficiency cannot be accounted for by a loss of long wavelength cones since the ERG and luminosity functions remain unaffected. Intracellular horizontal cell recordings in goldfish show that ethambutol hyperpolarizes all three types of cone driven horizontal cells and changes their color coding such that their spectral characteristics become cone-like as is the case in dark adapted retina. So, the initial effect induced by ethambutol seems to be an adaptation deficiency in color vision related tasks. Human wavelength discrimination and increment threshold spectral sensitivity functions obtained at low luminance levels are compared to behavioral functions in ethambutol treated goldfish. The high similarity between the ethambutol effects in man and goldfish, and the effects observed in the horizontal cell responses in goldfish are highly indicative that horizontal cells play a key role in color vision. So far their function has been puzzling.

Animals↗
PubMed1984

Effect of a chelating drug on balance and tissue distribution of four essential metals.

Numerous drugs have structures that suggest that they and/or their metabolites are chelating agents, and therefore might affect trace metal metabolism. Ethambutol, used therapeutically in the treatment of tuberculosis, is an example. The objective of this study was to determine the effects of ethambutol on tissue concentrations and balance of 4 essential trace metals: copper, iron, manganese, and zinc. Eighteen male Sprague-Dawley rats (148 +/- 7 g) were housed individually in metabolic cages. Six rats received ethambutol (400 mg/kg/day) via the drinking water. There were 2 control groups of 6 rats each, an ad-lib and a pair-fed group. Iron concentrations in kidney, liver, heart, and spleen were significantly increased in both the pair-fed and ethambutol-dosed rats, an effect related to reduced food intake. However, the total iron content of these organs was comparable to that of the ad-lib controls, suggesting retention of iron by these organs with reduced food intake during growth. Trace element balance was not affected by ethambutol administration. Ethambutol produced significant decreases in heart copper, kidney zinc, plasma zinc, and liver copper and zinc not due to the associated reduced food intake. The latter results support the hypothesis that chelating drugs may alter trace metal metabolism.

Animals↗