Gosling Roly D, Heifets Leonid, Gillespie Stephen H
Department of Medical Microbiology, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
J Antimicrob Chemother. 2003 Sep;52(3):473-6. doi: 10.1093/jac/dkg345. Epub 2003 Jul 29.
A model for evaluating the potency of a new anti-tuberculosis drug or a drug combination, based on a decline in the number of viable tubercle bacilli in patient's sputum during 5 days mono-therapy has been reported. One popular measure is based on the analysis of the decline in bacterial counts during the first 48 h of therapy and has been called early bactericidal activity (EBA). Such analyses could detect EBA for only a few drugs and were subject to variations in results obtained in different sites. To address these problems we applied a reiterative exponential decay model to evaluate the data on bacterial counts during 5 days of mono-therapy. The validity of this approach was tested using data from three previously published studies. For patients treated with isoniazid 300 mg daily, the values for the time taken to reduce the viable count by 50% (vt50) measured in days were, from a Kenyan study 0.58 days S.E.M. 0.18, from a Tanzanian study 0.41 days S.E.M. 0.04, and from a United States study 0.55 days s.e.m. 0.12. These differences were not statistically significant (P = 0.77 Kruskal-Wallis non-parametric ANOVA). Mean values of vt50 for all of the major anti-tuberculosis agents showed that there was an overlapping spectrum of activity from isoniazid 300 mg (vt50 0.58 days) to para-amino-salicylic acid (vt50 2.9 days) The variation between column means was greater than could be expected by chance (P = 0.0002 Kruskal-Wallis non-parametric ANOVA). From this, we conclude that the reiterative exponential decay model permits comparison between the data obtained in different centres and would allow the activity of a new drug to be compared with that of the currently available agents.
据报道，有一种基于患者痰液中活结核杆菌数量在5天单药治疗期间下降情况来评估新型抗结核药物或药物组合效力的模型。一种常用的测量方法是基于治疗前48小时细菌计数下降情况的分析，被称为早期杀菌活性（EBA）。此类分析仅能检测少数几种药物的EBA，且不同地点获得的结果存在差异。为解决这些问题，我们应用了迭代指数衰减模型来评估单药治疗5天期间的细菌计数数据。使用三项先前发表研究的数据对该方法的有效性进行了测试。对于每日服用300毫克异烟肼的患者，以天为单位测量的将活菌计数降低50%（vt50）所需时间的值，在肯尼亚的一项研究中为0.58天，标准误为0.18；在坦桑尼亚的一项研究中为0.41天，标准误为0.04；在美国的一项研究中为0.55天，标准误为0.12。这些差异无统计学意义（P = 0.77，Kruskal-Wallis非参数方差分析）。所有主要抗结核药物的vt50平均值表明，从300毫克异烟肼（vt50为0.58天）到对氨基水杨酸（vt50为2.9天）存在重叠的活性谱。各列平均值之间的差异大于偶然预期（P = 0.0002，Kruskal-Wallis非参数方差分析）。据此，我们得出结论，迭代指数衰减模型允许对不同中心获得的数据进行比较，并能将新药的活性与现有药物的活性进行比较。
