抗結核剤の試験管内作用に対する金属イオンの影響と錯塩形成との関連 (第1報)

抗結核剤に対する金属イオンの影響

抄録

The growth inhibiting concentration of p-aminosalicylic acid (PAS), isonicotinic acid hydrazide (INAH), thioacetazone (TB-1), streptomycin (SM), and dihydrostreptomycin (DHSM) in a Kirchner medium containing 10% horse serum against human-type tubercle bacilli H37Rv strain and its resistant strains to INAH, TB-1, SM, and DHSM, and PAS, is sometimes affected by the addition of excess of Ca, Cu, Ni, Fe (III), Al, Hg, Mg, Zn, Mn, Cd, and Co (II). The effect is either synergism or antagonism. The difference between synergism, antagonism, and no-effect occurs by the difference in the combination of antitubercular agents, the kind of metal used, and sensitivity or resistance of the bacillus used. The combination effective to sensitive strains may not affect resistant strains or simply remain effective. Sometimes, the combination may affect only the resistant strains. Detailed examination of the synergism-antagonism caused by different concentrations of the metal indicated that higher the concentration of the metal, the stronger was synergism while antagonism was found within a narrow concentration range of a combination of SM or DHSM and aluminum. The molar ratio of the antitubercular agent and metal combination which showed synergism was 5-0.005:1 in sensitive strains and 518-5:1 in resistant strains. In a combination of SM and mercury, this ratio was 0.5-0.15:1 in sensitive strains and 518-168:1 in resistant strains. The minimum effective concentration of mercury in such cases was 3.4×10^-6 M and 1.1×10^-6 M. The present experimental results would not support the hypothesis that the direct action of a metal on bacillus or a metal complex salt is effective.