非定型抗酸菌に関する研究

Although it has been proposed that atypical mycobacteriosis developed after a prolonged chemotherapy for pulmonary tuberculosis may due to the microbial alternation, convincing proof for this is not yet obtained.<BR>The present study wa s designed to clarify whether an appropriate combination of antituberculosis drugs, when administered to the mice infected both with tubercle bacilli and atypical mycobacteria, enables the latter to survive solely in vivo.<BR>Experiment I. Mice of dd-N strain were injected intraveno u sly with a mixture of each mg of strain H₃₇Rv and strain Mori, non-photochromogen. They were divided into 0t. w1o groups; one served as 'a control without chemotherapy and the other received two successive combined regimens of chemotherapy with the following daily doses: INH 0.1 mg SM 0.4 mg CS 0.15 mg for the first one and half months and KM 0.8 mg EB O.5 mg PAS 4 mg for the next five and half months. These combinations were devised on the basis of a previous experimente, which showed the therapeutic effect of seven months' single administrati on of drugs on mice infected with strain Mori as follows: INH, slight or no; SM, marked; CS, KM, EB, and PAS, adverse (i. e. worse). Animals were sacrificed three, five, and seven months after injection and viable bacterial units contained in each 1 mg tissue of lungs and spleen were calculated by Ogawa's method for quantitative cultivation. The nonphotochromogens were differentiated from tubercle bacilli by growth on media containing 1 mcg/ml PAS. The results were summerized in Table 1. The ratio of nonphotochromogens to tubercle bacilli in the spleen of the control mice tended to decrease gradually whereas the ratio in the treated animals maintained a very high level throughout the whole period of chemotherapy. On the other hand, all the bacilli obtained from the lungs of the control mice at three and five months were tubercle bacilli, but the ratio of nonphotochromogens to tubercle bacilli in the lungs of the treated animals increased gradually and reached to the high level after seven months of chemotherapy.<BR>Experiment II. Male mice, dd-N strain, were injected intravenously with a mixture of each 0.1 mg of nonphotochromogens strain Morita and strainH₃₇Rv. They were divided into two groups one week later; one without treatment and the other treated with two successive regimens of chemotherapy consisting of INH 0.1 mg + SM 0.4 mg EB 0.5 mg for two months and then INH0.1mg + PAS 4 mg + CS 0.15mg sulfamethoxypyrazine (SF) 0.4 mg for two and half months. In the previous experiment therapeutic effects of the single use of drugs for four and half months on mice infected with strain Morita were as follows: INH, adverse; SM, marked; EB, slight; PAS, adverse; CS, slight; and SF, adverse. Animals were s acrificed two, three and half, and four and half months later. Differential viable counts were made on the lungs and spleen as described in Exp.1. As shown in Table 2, almost all the bacilli recovered from the lungs and spleen of the control mice especially from the latter were tubercle bacilli. On the contrary, the tissues of the treated mice were or became almost occupied by the nonphotochromogens at the later stage. Drug sensitivity tests were carried out on colonies isolated from the treated and non-treated animals after four and half months observation. Colonies grown on PAS medium were regarded as nonphotochromogens and those of R-form on drug-free medium as tubercle bacilli. Table 3 shows that all the tested colonies, ecept one, were very similar in their drug-susceptibility to their original strains, i. e. strain Morita and H₃₇Rv. One colony, c.2, was found to be a mixture of tubercle bacilli and nonphotochromogens.