Umezawa, Ueda, Maeda and others1) isolated an antibiotic from the cultured liquid of a streptomyces which was assigned to a new species, Streptomyces kanamyceticus, and named this antibiotic kanamycin. This antibiotic is one of those discovered by their systematic screening studies for the antibiotics which are water-soluble, basic and have no delayed toxicity. They considered that water-soluble, basic and low toxic antibiotics without any delayed toxicity would be equally effective both in vitro and in vivo, especially against tubercle bacilli. Their consideration was based on examples such as streptomycin, fradiomycin and viomycin. Kanamycin was an antibiotic of this category, and inhibited growth of Gram negative and positive bacteria including nonpathogenic mycobacteria. As shown by Takeuchi and others2), it was low in acute and chronic toxicities to experimental animals including mice, rats, rabbits and dogs. They also examined the absorption the blood level, the distribution among various organs and the excretion of this antibiotic in rabbits. To our particular interest, it was also proved that kanamycin worked against a streptomycin-resistant variant of E. coli at the same concentration as that against the sensitive parent strain.
These informations were sufficient to stimulate us to an attempt examine whether or not this antibiotic is likewise effective against virulent tubercle bacilli in vitro and further experimental tuberculosis in mice. This paper describes the results on the effect of the antibiotic on virulent tubercle bacilli in vitro and in mice. The potency of kanamycin has been decided by Umezawa to be expressed by the weight of its free base. According to this definition, mcg or mg of kanamycin shown in this paper indicates the weight of kanamycin free base contained in the material used for experiments.
In the previous paper, the growth inhibitory action of kanamycin against tubercle bacilli in vitro and in mice was reported. The effect of this new antibiotic was striking and almost comparable with streptomycin. Thus, this agent has become the first promising substance ever brought into our examination since 1948. Although use of mice for the screening test of presumed antituberculous agents is a general trend of recent years, a historical survey of the literatures of streptomycin, paraaminosalicylic acid, 4-acetylaminobenzaldehyde thiosemicarbazone and isonicotinic acid hydrazide shows that the final decision of the efficacy must be done according to the guinea pig experiment.
In this connection, the present authors designed a large scale of guinea pig experiment as will be reported in the subsequent papers. Before entering into the experiment, however, a preliminary trial was undertaken in a smaller scale in order to grasp the outlook of the main experiment. The result was described in this paper as follows.
A white crystalline antibiotic inhibiting bacteria and fungi, especially mycobacteria and spore bacilli, was isolated from a streptomyces and was named mycospocidin. Chemical and physical properties differentiated it from known antibiotics. The present paper describes characters of mycospocidin-producing organism, isolation, physicochemical and biological properties of this antibiotic.
Duggar, et al. had originally described the characters of S. aureofaciens in their patent as seen also in Waksman’s book2) and they reported its variation range on various media. 3, 4 Boretti, et al5). and Scotti, et al6). had reported cultural or cytological studies of S. aureofaciens with regards of chlortetracycline production.
The author isolated producers of chlortetracycline from soil and examined their cultural characters and cytological features of those organisms. In this paper, he presents the identity of his organisms with S. aureofaciens and some cultural and cytological findings which could be concerned with antibiotic production.
The occurrence of double-drug-resistant Mycobacterium tuberculosis as strains simultaneously resistant to streptomycin and PAS or to isoniazid and PAS can be never or rare occurrence in patients who have received combined chemotherapy for pulmonary tuberculosis. The problem of triple-drug-resistance appears now very important in these patients having double- drug-resistant organisms. The present paper concerns this problem, i. e., the appearance rate of tirple-drug-resistant mutants in strains of M. tuberculosis simultaneously resistant to streptomycin and PAS or to isoniazid and PAS.
Mutation to triple-drug-resistance in strains simultaneously resistant to streptomycin and isoniazid has been previously studied by one of us1).