Tuberc Respir Dis.  1973 Sep;20(3):17-33. 10.4046/trd.1973.20.3.17.

Study on the Pathogenicity for Mice of Resistant Tubercle Bacilli Isolated from Patients under Treatment

Abstract

Forty-four strains of tubercle bacilli were isolated from patients under treatment at the Health Center from April 1971 to December 1971. The bacilli were examined for resistance to primary antituberculous drugs, INAH, PAS and SM. Each of the strains exhibiting various degrees of resistance was inoculated intravenously into 3 mice in an attempt to study the pathogenicity of the bacilli for the mice. These mice were sacrified 12 weeks after inoculation. The results obtained were as follows: a. The rate of resistance of tubercle bacilli by duration of treatment. For 6 months of treatment, the resistance to concentrations of IN AH 0.2 mcg or more, PAS 1 mcg or more and SM 1 mcg or m,ore was 46. 2, 62.5 and 92.3 percent respectively. For 7 to 24 months treatment, the resistance was 100 percent for all drugs. For 25 months or more treatment, the resistance was 83.3 percent in INAH, 91.7 percent in PAS and 100 percent in SM. b. The bacilli with increased resistance to INAH were found to have lowered pathogenicity for mice inversely. Even the bacilli with high resistance to INAH (50 mcg/ ml) did not always show a reduction in pathogenicity for mice. The bacilli with resistance to 10 mcg or more of PAS and SM showed a slight decrease of pathogenicity. but with resistance to 5 mcg of PAS and SM, there was marked virulence as high as sensitive strains. The bacilli with high resistance to PAS(l00mcg/ ml) showed marked reduction in virulence for mice, while the bacilli with high resistance to SM C100 mcg/ ml) were slightly reduced. c. Pathogenicity of dual resistance bacilli. Among the bacilli with resistance to two drugs, the bacilli with resistance to INAH 5mcg, PAS 10 mcg, and SM 10 mcg showed a slight reduction in virulence without regard to the degree of resistance to other drugs. The baci1li resistant to PAS 5 mcg and SM 5 mcg seemed to be more pathogenic. 'The bacilli with high resistance to both of these drugs did not show any lesions. d. Pathogenicity of the bacillì resistant to three drugs. Generally, the baci1li resistant to three drugs showed proportionate reduction with increasing resistance to INAH. The pathogenicity of the baci1li accompanied with resistance to PAS 5 mcg and SM 5mcg, was as high as the sensitive strain, without regard to the degree of resistance to other two drugs (with the exception of high resistance to both drugs), highly resistant bacilli to 2 drug combinations among the three drugs did not show any lesions in mice. e. Correlation between the pathogen,nicity and catalase activity. The virulence for mice was increased remarkably in bacilli exhibiting strong catalase activity while reduced conspicuously in moderàte and weak bacilli in catalase activities.

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