Two Groups of Mycobacterium avium Complex Strains Determined According to the Susceptibility to Rifampicin and Ansamycin

Abstract

Mycobacterium avium complex strains previously not exposed to any antituberculosis agents could be divided into two groups according to their susceptibility to rifampicin and ansamycin; one group susceptible to 80 ,ugiml rifampicin and to 1.25 ,ugiml ansamycin, and another resistant to these concentrations. In each group, the ratio of the minimal inhibitory concentration of ansamycin against that of rifampicin was greatly different depending on the strain. This naturally occurring resistance to rifampicin and ansamycin was frequently correlated to naturally occurring resistance to ethambutol, kanamycin, enviomycin, kitasamycin, and minocycline, but not correlated to that to isoniazid and sulfadimethoxine. Ansamycin was more active than rifampicin against M. bovis, M. kansasii, M. marinum, M. xenopi, and M. haemophilum.Ansamycin is a derivative of rifamycin SV (4, 7, 12). Its in vitro activity against Mycobacterium avium complex was reported by Woodley and Kilburn (21), Ungheri et al (20), Cynamon (3), and Heifets and Iseman (5). It inhibited the growth of the M. avium complex strains at concentrations of 1 to 2 ,ug/ml in the 7H-10 agar, 7H-10 broth, or 7H-11 agar medium (3,5,20,21). Therefore, ansamycin is at present the most promising agent for the treatment of disease due to the M. avium complex, which is resistant to most antituberculosis agents. However, the cross-resistance relationship between rifampicin and ansamycin (both are derivatives of rifamycin SV) is not yet clear. Employing the 7H-11 agar medium, Heifets and Iseman (5) reported that all strains that were susceptible to 1.0 ,ug/ml rifampicin were susceptible to 0.5 ,ug/ml ansamycin and 20% of the strains, which were naturally resistant to 10 dug/ml rifampicin, were susceptible to 0.5 iug/ml ansamycin. Only 10% of the latter strains were resistant to 2.0 eug/ml ansamycin. Their finding suggests that the cross-resistance relationship between these two agents is only partial. The present study has been carried out to clarify the cross-resistance relationship. 615

Different Correlations of Drug Susceptibilities to Colonial Morphology in Mycobacterium avium Complex Strains

“…Successively, several authors (5-7) reported that the SmT colonial morphology correlated with resistances to rifampicin, streptomycin, kanamycin, and viomycin, and the SmD colonial morphology with susceptibilities to these drugs. Tsukamura (14,15) observed that the M. avium complex strains are divided into two groups, one resistant to most antituberculosis drugs and another susceptible to these, and that such resistances or susceptibilities well correlated with clinical effect of chemotherapy. Moreover, it was observed that the resistances or susceptibilities to rifampicin, minocycline, streptomycin, kanamycin, enviomycin, and kitasamycin in M. avium complex strains isolated from patients previously not treated by any antituberculosis drugs do not appear at random but do appear showing correlations to each other (16).…”