BACTERICIDAL ACTIVITY OF ANTITUBERCULOSIS DRUGS AGAINST MYCOBACTERIUM AVIUM COMPLEX

Abstract

The bactericidal activity of antituberculosis drugs against two strains of M. avium complex 13008 (serotype 20) and 13016 (serotype 4), was observed using modified Dubos liquid medium (1.3 g of Dubos Broth Base (Difco) in 180 mil of distilled water plus 20 ml of bovine serum). The strains were most susceptible to antituberculosis drugs among M. avium complex strains (Table). The test strains were cultivated in Ogawa egg medium at 37°C for 10 days, and growing colonies were homogenized by shaking with glass beads for 10 minutes and suspended in the modified Dubos liquid medium to a concentration of 2 mg wet weight per ml. The media containing drug and containing no drug were incubated at 37°C for 24 hours under shaking (8 cm-moving range and 56 strokes per minute). After incubation, the medium was diluted by a 0.1 % Tween 80 aqueous solution to 10^-7, and each 0.02 ml-sample of 10^-4 to 10^-7 suspensions was inoculated onto Ogawa egg medium. The Ogawa egg medium slants were incubated at 37°C for 28 days, and the number of colonies was counted. The bactericidal activity was determined as a ratio of the number of colony forming units in 10 ml aliquot of drug-containing Dubos liquid medium against the number of colony forming units in the control Dubos liquid medium.
The results are shown in Figures 1 and 2.Under the condition tested, rifampicin, isoniazid, ethambutol, ethionamide and cycloserine did not exhibit any bactericidal activity, and only streptomycin and enviomycin exhibited bactericidal activity. It was remarkable that, although the susceptibility of these two strains to rifampicin was similar to that of M. tuberculosis to rifampicin, rifampicin did not exhibit bactericidal activity on these M. avium complex strains. Under the same condition, most antituberculosis drugs, rifampicin, isoniazid, streptomycin and enviomycin exhibited bactericidal activity on M. tuberculosis (Tsukamura, M., Mizuno, S., Toyama, H., and Ichiyama, S.: In vitro bactericidal activity of antituberculosis agents on Mycobacterium tuberculosis. Kekkaku 62: 295-298, 1987). Absence of bactericidal activity of rifampicin and isoniazid against M. avium complex seems to explain the fact that infection caused by M. avium complex is difficult to cure and often shows relapse.