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A new antituberculosis agent, ofloxacin (DL8280), inhibited the growth of Mycobacterium tuberculosis at concentrations of 0.63 to 1.25 micrograms/ml. There were no cross-resistance relationships between this agent and other antituberculosis agents. The agent delayed the growth rate of M. tuberculosis (strain H37Rv) at concentrations of 0.2 to 0.5 microgram/ml. It showed considerable bactericidal activity at concentrations a little higher than the growth-inhibitory concentration. The combined effect with other antituberculosis agents seemed to be additive. The pattern of resistance that developed with this agent was the obligatory two-step pattern, and there were 2 resistant phenotypes.

In Mycobacterium avium complex strains, which were not exposed previously to any antituberculosis drugs, resistances to rifampin, minocycline, and kitasamycin, and resistances to streptomycin and kanamycin appeared frequently in the same strains. These data indicate that patterns of drug resistance in these organisms are not random but occur through linked mechanisms.

Ofloxacin (DL 8280) is rapidly eliminated from mouse organs. It disappears quickly from the lungs and the spleen and more slowly from the liver and the kidneys. The antituberculosis activity of this agent was shown in mice when the agent was given intraperitoneally at daily doses of 1 mg per mouse (approximately 42 mg/kg). The number of viable bacteria of Mycobacterium tuberculosis strain H37Rv contained in the liver decreased markedly in the mice treated with ofloxacin, and the inhibitory effect of the agent seemed to appear when the tubercle bacilli actively multiplied.

Successful chemotherapy of pulmonary disease caused by Mycobacterium avium complex by antituberculosis drugs has been reported by a number of investigators. However, no certain evidence of the efficacy has yet been demonstrated in a controlled clinical trial. The present study has approached this problem in 2 ways: serial analysis of minimal inhibitory concentrations (MIC) during treatment and correlation of response to therapy with initial MIC. It was observed that after administration of antituberculosis drugs (rifampin, isoniazid, kanamycin, enviomycin, and minocycline), MIC values for the M. avium complex strain increased significantly. This change may be considered a result of suppression of relatively susceptible bacteria and as evidence of the efficacy of drugs. Furthermore, a correlation between the MIC values determined before chemotherapy with the conversion of sputum to negative was shown. The M. avium complex strains varied markedly in their susceptibility to antituberculosis drugs, and these susceptibilities were correlated with the chemotherapeutic effect. The fate of patients seemed to be greatly influenced by the susceptibilities of the strains that caused infection.

The epidemiology of mycobacterial disease in Japan changed considerably over the period 1971 to 1984. During this time, the incidence of pulmonary disease caused by Mycobacterium tuberculosis has steadily declined; disease caused by M. avium complex has remained stable; disease caused by M. kansasii has increased considerably; and, for the first time, substantial numbers of cases caused by M. szulgai, M. fortuitum, M. chelonae, and M. nonchromogenicum have been reported. From 1981 to 1984 the incidence of pulmonary nontuberculous mycobacterioses (NTM) was estimated at 1.73 +/- 0.25 cases per 100,000 population per year; of these, M. avium complex constituted 1.29 +/- 0.24 and M. kansasii 0.34 +/- 0.11 per 100,000 per year. The prevalence of the NTM was relatively high in southwestern Japan (industrialized, warm climate) and low in northern Japan (rural, cold).

A new antibacterial substance, ofloxacin (DL8280), was used in the treatment of pulmonary tuberculosis. The agent was given to 19 patients with chronic cavitary lung tuberculosis as single doses of 300 mg daily for 6 to 8 months. A decrease in the amount of tubercle bacilli in the sputum was observed in almost all patients, and negative conversion occurred in 5. Resistance of tubercle bacilli to the agent appeared in patients who did not show negative conversion. No side effects were observed during the administration period. The agent was considered useful in lung tuberculosis therapy.