Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages
Bacteriostatic and bactericidal activities of benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium in human macrophages
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DOI：
10.1128/aac.40.6.1482
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发表时间：
1996-06-01
影响因子：
4.9
通讯作者：
Heifets, L
中科院分区：
文献类型：
--
作者：
Mor, N;Simon, B;Heifets, L
测定了KRM-1648对人单核细胞来源的巨噬细胞及细胞外M、结核和禽分枝杆菌的抑制和杀菌活性。KRM-1648对胞内外细菌的最低抑菌浓度(MIC)和最低抑菌浓度(MBCs)显著低于利福平。两种药物对胞内细菌的最低抑菌浓度和最低抑菌浓度仅为胞外细菌的两倍。本研究中发现的KRM-1648的长期作用可能与高的细胞内蓄积率有关，细胞内蓄积率是利福平的50到100倍，有必要进一步研究KRM-1648的细胞内分布和药物与巨噬细胞内细菌的实际相互作用部位，以及在长期巨噬细胞培养实验中评估KRM-1648与其他药物的联合作用。
Inhibitory and bactericidal activities of KRM-1648 were determined against Mycobacterium tuberculosis and M. avium residing in human monocyte-derived macrophages and extracellular M, tuberculosis and M. avium. MICs and MBCs of KRM-1648 against intracellular and extracellular bacteria were substantially lower than those of rifampin. The MICs and MBCs of either drug against the intracellular bacteria were only twofold lower than or equal to the values found for extracellular bacteria. The prolonged effect of KRM-1648 found in this study is probably associated with high ratios of intracellular accumulation, which were 50- to 100-fold higher than that found for rifampin, Further studies on intracellular distribution of KRM-1648 and on the sites of actual interaction between the drug and bacteria residing in macrophages are necessary, as well as evaluation of combined effects of KRM-1648 with other drugs in long-term macrophage culture experiments.