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首页> 外文期刊>Infection and immunity >Growth Inhibition of Mycobacterium tuberculosis After Single-Pulsed Exposures to Streptomycin, Ethambutol, and Rifampin
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Growth Inhibition of Mycobacterium tuberculosis After Single-Pulsed Exposures to Streptomycin, Ethambutol, and Rifampin

机译:单次暴露于链霉素,乙胺丁醇和利福平后,结核分枝杆菌的生长抑制

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It was reported earlier that the degree of growth inhibition of tubercle bacilli after single-pulsed isoniazid exposures is a function of the time-concentration product (TCP) of exposure rather than of either time or concentration alone (TCP = hr exposure × μg of drug/ml). In the present investigation, these time and concentration studies have been extended to streptomycin (SM), ethambutol (EMB), and rifampin (RMP). Mycobacterium tuberculosis H37Ra was grown in Sautons liquid medium at 37 C with aeration. Rapidly growing cells were harvested and resuspended at 0.5 to 0.6 mg (dry wt)/ml in fresh medium; incubation was continued in the presence of various concentrations of the appropriate drug. At time intervals, samples were diluted 1:200 into drug-free medium for turbidimetric growth assay. Minimal inhibitory concentrations of EMB, SM, and RMP were approximately 0.2, 0.02, and 0.002 μg/ml, respectively. When cells were pulsed with 0.0125 to 0.0625 μg of RMP per ml at time intervals of up to 9.5 hr, the degree of subsequent growth inhibition appeared to be a function of TCP. A similar relationship was observed when SM was tested over a range of 0.125 to 1.0 μg/ml and various time intervals of up to 8 hr. In contrast, inhibition of tubercle bacilli after EMB exposures was dependent primarily on exposure time and was affected only slightly by concentration. At any particular exposure time between 3 and 16 hr, 1.25 to 7.5 μg of EMB per ml produced similar levels of inhibition, but marked inhibition did not occur unless the exposure time exceeded 10 hr. Relationships of these latter findings to the mode of action of EMB and the potential clinical significance of the RMP, SM, and EMB data are discussed.
机译:早前有报道称,单脉冲异烟肼暴露后结核杆菌的生长抑制程度是暴露时间浓度乘积(TCP)的函数,而不是时间或浓度的函数(TCP = hr暴露×μg药物) / ml)。在本研究中,这些时间和浓度研究已扩展至链霉素(SM),乙胺丁醇(EMB)和利福平(RMP)。 结核分枝杆菌 H37Ra在Sautons液体培养基中于37°C曝气生长。收集快速生长的细胞,并以0.5至0.6 mg(干重)/ ml的浓度重悬于新鲜培养基中;在各种浓度的适当药物存在下继续温育。在一定的时间间隔内,将样品以1:200的比例稀释到无毒培养基中,以进行比浊法生长测定。 EMB,SM和RMP的最低抑菌浓度分别约为0.2、0.02和0.002μg/ ml。当以每毫升0.0125至0.0625μg的RMP以最多9.5小时的时间间隔对细胞进行脉冲处理时,随后的生长抑制程度似乎是TCP的函数。在0.125至1.0μg/ ml的范围内以及最多8小时的各种时间间隔内测试SM时,观察到相似的关系。相比之下,EMB暴露后对结核杆菌的抑制作用主要取决于暴露时间,并且受浓度的影响很小。在3至16小时之间的任何特定暴露时间下,每毫升1.25至7.5μgEMB产生相似的抑制水平,但是除非暴露时间超过10小时,否则不会发生明显的抑制作用。讨论了这些后期发现与EMB作用模式的关系以及RMP,SM和EMB数据的潜在临床意义。

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