Y-3118、左氧氟沙星和氧氟沙星单独或与乙胺丁醇联合应用对鸟分枝杆菌复合群的体外、人巨噬细胞内及米色小鼠体内活性。
Activities of bay Y 3118, levofloxacin, and ofloxacin alone or in combination with ethambutol against Mycobacterium avium complex in vitro, in human macrophages, and in beige mice.
作者信息
Bermudez L E, Inderlied C B, Kolonoski P, Wu M, Barbara-Burnham L, Young L S
机构信息
California Pacific Medical Center Research Institute, San Francisco 94115, US
出版信息
Antimicrob Agents Chemother. 1996 Mar;40(3):546-51. doi: 10.1128/AAC.40.3.546.
Levofloxacin, ofloxacin, and Bay Y 3118 are new fluoroquinolones with variable in vitro bacteriostatic and bactericidal activities against the Mycobacterium avium complex (MAC). The potential therapeutic activities of these agents both alone and combined with ethambutol were evaluated in a human macrophage test system and in the beige mouse animal test system with MAC strain 101. Bay Y 3118 at a human-equivalent dose of 30 mg/kg/day for 4 weeks caused a significant reduction in mortality compared with that in untreated controls (P = 0.02). Bay Y 3118 also caused significant reductions in the number of MAC organisms in the blood, liver tissue, and spleen tissue compared with those in untreated controls. Levofloxacin at a human-equivalent dose of 200 mg/kg/day was associated with a significant reduction in mortality (10 versus 39%); however, treatment with either levofloxacin or ofloxacin (200 mg/kg/day) did not result in significant reductions in the numbers of MAC organisms in blood, liver, and spleen compared with those in untreated controls. When Bay Y 3118 was combined with ethambutol, there was no enhancement in therapeutic activity except in the spleen in terms of CFU per gram (reductions of 89% compared with the untreated control, 63% compared with Bay Y 3118 alone, and 72.5% compared with ethambutol alone). Levofloxacin in combination with ethambutol was more active than either drug alone in the reduction of organisms in blood, liver, and spleen. Bay Y 3118 was the most active fluoroquinolone for monotherapy of MAC infection in beige mice, and the combination of ethambutol plus either levofloxacin or ofloxacin was at least additive. In summary, this study demonstrates that quinolones, although active, are inhibitory against MAC in vivo and that there is little correlation between the activity of quinolones in vitro and the activity in mice.
左氧氟沙星、氧氟沙星和Bay Y 3118是新型氟喹诺酮类药物，对鸟分枝杆菌复合体（MAC）具有不同的体外抑菌和杀菌活性。在人巨噬细胞测试系统和携带MAC菌株101的米色小鼠动物测试系统中，评估了这些药物单独使用以及与乙胺丁醇联合使用时的潜在治疗活性。与未治疗的对照组相比，Bay Y 3118以30 mg/kg/天的等效人剂量给药4周，可显著降低死亡率（P = 0.02）。与未治疗的对照组相比，Bay Y 3118还可显著减少血液、肝组织和脾组织中MAC菌的数量。左氧氟沙星以200 mg/kg/天的等效人剂量给药可显著降低死亡率（10%对39%）；然而，与未治疗的对照组相比，使用左氧氟沙星或氧氟沙星（200 mg/kg/天）治疗并未显著减少血液、肝脏和脾脏中MAC菌的数量。当Bay Y 3118与乙胺丁醇联合使用时，除了脾脏中每克菌落形成单位（CFU）外，治疗活性没有增强（与未治疗的对照组相比降低了89%，与单独使用Bay Y 3118相比降低63%，与单独使用乙胺丁醇相比降低72.5%）。左氧氟沙星与乙胺丁醇联合使用在减少血液、肝脏和脾脏中的菌量方面比单独使用任何一种药物都更有效。Bay Y 3118是米色小鼠中治疗MAC感染单药治疗最有效的氟喹诺酮类药物，乙胺丁醇与左氧氟沙星或氧氟沙星联合使用至少具有相加作用。总之，本研究表明喹诺酮类药物虽然具有活性，但在体内对MAC具有抑制作用，并且喹诺酮类药物的体外活性与在小鼠体内的活性之间几乎没有相关性。
Zotero 插件