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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概要

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• Although many authors have tried to induce drug resistance in experimental tuberculosis, they have not always succeeded in obtaining resistant tubercle bacilli.<BR>Different from any previous experiments, the author inoculated in the present study low resistant tubercle bacilli obtained in vitro to mice and observed the subsequent developement of drug resistance.<BR>H2 strain of tubercle bacilli was inoculated to Dubos medium containing 0.05γ/mlof INH or 1γ/ml of SM, and after 2 weeks' incubation in the former and 10 days' incubation in the latter, the resultant bacilli which became partially resistant to 0.5γ/ml of INH or completely resistant to 1γ/ml of SM were inoculated intravenously to white mice in 0.1mg dose. Two weeks after the infection, these animals received the treatment with relatively small dose of INH (0.2mg daily) or SM (0.4mg daily) for two months at the longest.<BR>The INH-and SM-resistances of the bacilli isolated from the lungs of mice were measured by 1% Ogawa medium.<BR>The results obtained were as follows:<BR>1) The strains isolated from the mice infected with sensitive H2-strain and treated with INH or SM, showed no resistance to these drugs.<BR>2) The strains isolated from the mice infected with INH-low resistant H2-strain and treated with INH alone, INH combined with cycloserine (CS), or INH combined with sulfisoxazole (SI).showed partial resistance to 5r of INH.<BR>Combined use of CS and SI presented no inhibitory effect to the resistance developement to INH.<BR>3) The strains isolated from the animals received combined treatments with SM and INH, SM, INH and SI, and SM, INH and disoxyl (DAT), revealed incomplete resistance to 10 of SM despite of the remarkable decrease of viable counts from the lungs, but there were not observed any bacilli resistant to 50 of SM such as seen in the case treated with SM alone, showing the inhibitory effect of the above combinations against the developement of resistance to SM.<BR>From the above results it is suggested that the survived bacilli after chemotherapy might become drug resistant inspite of the decrease of viability, and that the initial chemotherapy should be powerful enough to effect negative conversion of tubercle bacilli. Also a sufficient cares should be paid to the appearance of low resistant bacilli, even in the case without cavity.

• 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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