Metronidazole therapy in mice infected with tuberculosis

Metronidazole therapy in mice infected with tuberculosis
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DOI:
10.1128/aac.43.5.1285
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发表时间:
1999-05-01
影响因子:
4.9
通讯作者:
Orme, IM
Orme, IM
中科院分区:
医学2区
文献类型:
--
作者:
Brooks, JV;Furney, SK;Orme, IM

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用体外和体内小鼠模型检测甲硝唑对结核分枝杆菌生长的抑制作用。在体外,将甲硝唑添加到受感染的骨髓来源的巨噬细胞的培养中没有任何效果,也没有增加异烟肼引起的细菌负荷的减少。在体内,在疾病活动期、遏制阶段或长期异烟肼治疗(康奈尔模型)期间,甲硝唑没有减少气雾剂感染小鼠肺部的细菌数量。如果在雾化吸入100天后,在已确定的慢性病状态下给予甲硝唑治疗,则可以看到小幅但显著的减少。这些数据表明,在大多数情况下,结核分枝杆菌微生物不处于对甲硝唑作用敏感的代谢状态,因此,这种药物的临床价值有限。
The capacity of metronidazole to inhibit the growth of Mycobacterium tuberculosis was tested in in vitro and in vivo mouse models. In vitro addition of metronidazole to cultures of infected bone marrow-derived macrophages had no effect, nor did it increase the reduction in bacterial load due to isoniazid. In vivo, metronidazole did not reduce bacterial numbers in the lungs of aerosol-infected mice during the active stage of the disease, during a phase of containment, or after prolonged isoniazid therapy (Cornell model). A small but significant reduction was seen if metronidazole therapy was given during an established chronic disease state 100 days after aerosol administration. These data indicate that under most conditions M. tuberculosis organisms are not in a metabolic state in which they are susceptible to the action of metronidazole and, hence, that this drug would be of limited clinical value.