De Jager Veronique, van der Merwe Lize, Venter Amour, Donald Peter R, Diacon Andreas H
Task Applied Science, Tuberculosis Clinical Research Centre, Bellville, Cape Town, South Africa.
Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa.
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02088-16. Print 2017 Apr.
Recent early bactericidal activity (EBA) studies of isoniazid-based antituberculosis therapies have shown a lower EBA over the first two treatment days than in earlier years. To quantify this trend and evaluate factors contributing to it, we extracted individual data from 18 studies with a total of 182 participants using isoniazid-containing therapies between 1992 and 2015 at a single site and laboratory in Cape Town, South Africa. We recalculated EBA as the daily fall in CFU per milliliter sputum up to day 2 of therapy (EBA) for individual patients and treatment groups and used mixed-effects linear models to investigate the correlation between pretreatment CFU, EBA, and year of study. We found that mean pretreatment CFU and year of study accounted for 46% and 47%, respectively, of the variation in mean EBA Mean pretreatment CFU differed between the periods 1992 to 2001 and 2007 to 2015 by 0.92 log CFU (95% confidence interval [CI], 0.57 to 1.28; < 0.0001). On average, pretreatment CFU dropped by 0.053 log CFU (95% CI, 0.029 to 0.076; = 0.0004) and EBA by 0.012 log CFU (95% CI, 0.006 to 0.018; = 0.001) per year. The EBA of isoniazid-based antituberculosis therapy is strongly correlated with baseline mycobacterial load and shows a declining trend over the past 2 decades.
近期关于基于异烟肼的抗结核治疗的早期杀菌活性（EBA）研究表明，在治疗的头两天，其EBA较前些年有所降低。为了量化这一趋势并评估导致该趋势的因素，我们从18项研究中提取了个体数据，这些研究共有182名参与者，于1992年至2015年期间在南非开普敦的一个地点和实验室接受含异烟肼的治疗。我们将EBA重新计算为治疗第2天前每位患者和治疗组每毫升痰液中CFU的每日下降量（EBA），并使用混合效应线性模型来研究治疗前CFU、EBA和研究年份之间的相关性。我们发现，治疗前CFU均值和研究年份分别占EBA均值变异的46%和47%。1992年至2001年期间与2007年至2015年期间的治疗前CFU均值相差0.92 log CFU（95%置信区间[CI]，0.57至1.28；<0.0001）。平均而言，每年治疗前CFU下降0.053 log CFU（95%CI，0.029至0.076；=0.0004），EBA下降0.012 log CFU（95%CI，0.006至0.018；=0.001）。基于异烟肼的抗结核治疗的EBA与基线分枝杆菌载量密切相关，并且在过去20年中呈下降趋势。
