EXPERIMENTAL STUDIES ON THE DEVELOPEMENT OF DRUG RESISTANCE IN VIVO:Part 2. Studies on the Developement of Kanamycin (KM) and Ethionamide (TH) Resistance in Experimental Tuberculosis in Mice

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概要

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• It was previously reported that a marked developement of INH-and SM-resistance was observed in experimental tuberculosis in mice infected with low resistant tubercle bacilli obtained in vitro.<BR>In the present paper, studies on the developement of KM-and TH-resistance in vivo was carried out under the same condition as that previously reported.<BR>H<SUB>2</SUB> strain of tubercle bacilli was inoculated to Dubos medium containing 1γ/m<I>l</I> of KM or 1γ/m<I>l</I> of Th, and after 10 days' incubation in the former and 2 weeks' incubation in the latter the resultant bacilli which became incompletely resistant to 1γ/ml of KM or to 5γ/m<I>l</I> of Th were injected intravenously to mice in 0.1mg amount. Two weeks after the infection, the treatment of these animals were started by administering relatively small dose of KM (0.8mgdaily) or Th (0.2mg daily) for 3 (KM) and 2 (Th) months at the longest.<BR>The resistance of isolated bacilli was measured by Youmans medium for KM and by You mans medium and modified Kirchner agar medium for Th.<BR>The results obtained were as follows.<BR>1) The strains isolated from the mice infected with sensitive H<SUB>2</SUB>-strain and treated with KM or TH, showed no resistance to these drugs.<BR>2) The strains isolated from the mice infected with KM-low resistant H<SUB>2</SUB>-strain and trea ted with KM alone, KM combined with cycloserine (CS), and KM combined with sulfisoxazole (SI), showed partial resistance to 10γ of KM. Combined use of CS and SI presented no inhibitory effect to the resistance developement of KM.<BR>3) The strains isolated from the mice infected with TH-low resistant H<SUB>2</SUB>-strain and treated with TH alone, showed partial resistance to 20γ of TH.<BR>The strains isolated from the animals received combined treatments with Th+CS, Th+SI, Th+KM and Th+KM+CS, revealed the resistance to 20γ of Th in spite of the marked decrease of the viable counts from the lungs.<BR>The combined use of CS, SI, KM, KM+CS with Th effected only a slight retardation of resistance developement to Th.<BR>These results suggests that also in the use of secondary drugs the negative conversion of tubercle bacilli in the early stage should be an important aim and that sufficient cares must be paid to the appearance of low resistant bacilli.

• 一般社団法人 日本結核病学会の論文

著者

• 木村 仁

  東京大学伝染病研究所内科学研究部

関連論文

• EXPERIMENTAL STUDIES ON THE DEVELOPEMENT OF DRUG RESISTANCE IN VIVO:Part 2. Studies on the Developement of Kanamycin (KM) and Ethionamide (TH) Resistance in Experimental Tuberculosis in Mice
• EXPERIMENTAL STUDIES ON THE DEVELOPEMENT OF DRUG RESISTANCE IN VIVO:Part I. Studies on the Developement of Hydrazid (INH) and Streptomycin (SM) Resistance on Experimental Tuberculosis in Mice

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