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Isoniazid inhibited the growth of Mycobacterium avium-Mycobacterium intracellulare strains at concentrations of 0.1-25 micrograms/ml and was even bactericidal for several strains. The bactericidal activity was observed in relatively susceptible strains. The susceptibility did not correlate with colonial morphology but correlated with species identification. Mycobacterium avium strains were more resistant to isoniazid than Mycobacterium intracellulare strains.

Treatment of nontuberculous mycobacterial infection should be carried out by the chemotherapeutic regimens most suitable for each species. We performed in-vitro susceptibility tests for various species and determined the probability in which the mycobacteria of each species are inhibited by blood concentrations attainable by the dosages usually used. From such determinations, the following regimens have been recommended: 1) M. avium-M. intracellulare complex, Rifampicin + Enviomycin + Ethambutol; 2) M. kansasii, Ofloxacin + Enviomycin + Rifampicin; 3) M. szulgai, Enviomycin - Ethambutol + Isoniazid; 4) M. fortuitum, Ofloxacin. The effectiveness of the treatment of the infection caused by M. avium complex is less than 15% even using the above regimen, while it is high in the treatment of infections caused by M. kansasii and M. szulgai. There are no effective regimens for the treatment of infection caused by M. chelonae or M. simiae. The above recommendations are useful in practice, because, at present, reliable susceptibility testing of nontuberculous mycobacteria is not yet done commonly.

In this study, it was investigated whether or not Mycobacterium avium complex strains were inhibited by such low concentrations of isoniazid and ethionamide as possible in blood. The inhibitory concentrations were determined by the "Actual Count" method (Tsukamura, M.: Japan J. Tuberc. 12: 46-54, 1964), in which the inhibitory concentration was measured as a concentration that can inhibit the growth of 'countable' colony-forming units. The ratio of strains which were inhibited by such low concentrations as 0.2 microgram/ml isoniazid or 5 micrograms/ml ethionamide was 14%. The result suggests that there are some strains in which isoniazid or ethionamide are clinically effective, though their prevalence was low (14%).

Comparing minimal inhibitory concentrations (MICs) determined in various nontuberculous mycobacteria with those for Mycobacterium tuberculosis strains, which were isolated from patients who were untreated previously by any antituberculosis drugs, clinical efficacy of isoniazid and ethambutol in the treatment of nontuberculous mycobacteriosis was evaluated. The MICs of isoniazid for M. tuberculosis strains were 0.03-0.1 microgram/ml, whereas the MICs for M. xenopi strains were 0.1-0.4 microgram/ml, those for M. szulgai 0.2-0.8, and those for M. kansasii 0.8-1.6 micrograms/ml. The fact that M. xenopi strains are susceptible to isoniazid was reported previously, and in this study, it was shown that M. szulgai and M. kansasii are also considerably susceptible to isoniazid. Isoniazid may be useful in the treatment of infection due to these mycobacteria. The MICs of ethambutol for M. tuberculosis strains ranged from 0.8 to 3.13 micrograms/ml. The percentages of strains of various mycobacteria, which are susceptible to 3.13 micrograms/ml ethambutol, were 100% in M. szulgai, 100% in M. nonchromogenicum, 90% in M. gordonae, 88% in M. marinum, 77% in M. kansasii, 46% in M. malmoense, and 30% in M. scrofulaceum. In contrast, the percentage in M. avium complex strains remained only 19%. It has been suggested that ethambutol is effective in the treatment of diseases caused by M. szulgai, M. marinum and M. kansasii.