Abstract
The spiro-piperidyl rifamycins are newly synthesized rifamycin S compounds. One of these compounds, LM 427, was tested in vitro against strains of the M. avium complex and strains of M. tuberculosis; LM 427 inhibited 81.3% of 155 strains of M. avium complex tested at a concentration of 1.0 .mu.g/ml compared with 5.8% inhibited by the same concentration of rifampin. Twenty-nine strains were resistant to both LM 427 and rifampin at 1.0 .mu.g/ml. Further testing of these 29 strains showed LM 427 inhibitory for all but 5 strains at 2.0 .mu.g/ml and 11 strains at 5.0 .mu.g/ml. Rifampin inhibited none at 2.0 .mu.g/ml and 11 strains of 5.0 .mu.g/ml. The in vitro activity of LM 427 was also compared with rifampin by testing both compounds against M. tuberculosis at 1.0 .mu.g/ml. This comparison showed that all strains susceptible to rifampin were also susceptible to LM 427; 16 strains were susceptible to LM 427 and resistant to rifampin. The inhibition of drug-resistant mycobacterial species that cause human pulmonary disease makes this compound an important consideration for future clinical studies.