Woodley C L, Kilburn J O
Am Rev Respir Dis. 1982 Sep;126(3):586-7. doi: 10.1164/arrd.1982.126.3.586.
The spiro-piperidyl rifamycins are newly synthesized rifamycin S compounds. One of these compounds, LM 427, was tested in vitro against strains of the Mycobacterium avium complex and strains of M. tuberculosis; LM 427 inhibited 81.3% of 155 strains of the M. avium complex tested at a concentration of 1.0 microgram/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 microgram/ml. Further testing of these 29 strains showed LM 427 inhibitory for all but 5 strains at 2.0 micrograms/ml and inhibitory for all but 1 at 5.0 micrograms/ml. Rifampin, on the other hand, inhibited none at 2.0 micrograms/ml and 11 strains at 5.0 micrograms/ml. The in vitro activity of LM 427 was also compared with rifampin by testing both compounds against M. tuberculosis at 1.0 microgram/ml. This comparison showed that all strains susceptible to rifampin were also susceptible to LM 427. However, 16 strains were susceptible to LM 427 and resistant to rifampin. The inhibition of drug-resistant mycobacterial species that cause pulmonary disease makes this compound an important consideration for future clinical studies.
螺环哌啶基利福霉素是新合成的利福霉素S化合物。其中一种化合物LM 427在体外针对鸟分枝杆菌复合群菌株和结核分枝杆菌菌株进行了测试；在浓度为1.0微克/毫升时，LM 427抑制了所测试的155株鸟分枝杆菌复合群菌株中的81.3%，而相同浓度的利福平仅抑制了5.8%。有29株菌株对1.0微克/毫升的LM 427和利福平均耐药。对这29株菌株的进一步测试表明，在2.0微克/毫升时，除5株外，LM 427对所有菌株均有抑制作用；在5.0微克/毫升时，除1株外，对所有菌株均有抑制作用。另一方面，利福平在2.0微克/毫升时对所有菌株均无抑制作用，在5.0微克/毫升时仅抑制11株菌株。通过在1.0微克/毫升的浓度下用这两种化合物针对结核分枝杆菌进行测试，还比较了LM 427和利福平的体外活性。这种比较表明，所有对利福平敏感的菌株对LM 427也敏感。然而，有16株菌株对LM 427敏感但对利福平耐药。对引起肺部疾病的耐药分枝杆菌物种的抑制作用使得该化合物成为未来临床研究的重要考虑对象。
