Assessment of treatment response by colony forming units, time to culture positivity and the molecular bacterial load assay compared in a mouse tuberculosis model
Assessment of treatment response by colony forming units, time to culture positivity and the molecular bacterial load assay compared in a mouse tuberculosis model
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DOI：
10.1016/j.tube.2017.05.002
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发表时间：
2017-07-01
期刊：
影响因子：
3.2
通讯作者：
de Steenwinkel, Jurriaan E. M.
中科院分区：
文献类型：
--
作者：
de Knegt, Gerjo J.;Dickinson, Laura;de Steenwinkel, Jurriaan E. M.
本研究的目的是比较菌落形成单位（CFU）计数、阳性时间（TTP）测定和分子细菌负荷（MBL）测定，并探讨最后一种测定是否可以检测出不能在固体培养基上生长的亚群。使用CFU计数、UP和MBL测定来确定小鼠结核病模型的匹配肺样本中的分枝杆菌载量。小鼠用4个治疗组治疗24周：异烟肼（H）-利福平（R）-吡嗪酰胺（Z）、HRZ-链霉素（S）、HRZ -乙胺丁醇（E）或ZES。当比较CFU与MBL时，观察到正相关性。对CFU vs.时间、MBL vs.时间和1/TTP vs.时间进行细菌净消除描述，并通过非线性回归拟合。除HRZE外，CFU与时间和1/TTP与时间显示双相下降。基于α斜率，分别比较CFU与时间和TTP与时间（HRZE、HRZ、HRZS和ZES）发现相似的排序。相比之下，MBL与时间的关系显示出单相下降，消除梯度平坦，等级顺序分别为ZES、HRZ、HRZE和HRZS。方法之间的相关性反映了每种方法辨别一般分枝杆菌负荷的能力。基于净消除的描述，我们得出结论，MBL检测试剂盒可以检测CFU或TIP检测试剂盒无法检测到的结核分枝杆菌亚群。(C)2017作者爱思唯尔有限公司出版
The aim of the study is to compare counting of colony forming units (CFU), the time to positivity (TTP) assay and the molecular bacterial load (MBL) assay, and explore whether the last assays can detect a subpopulation which is unable to grown on solid media. CFU counting, UP and the MBL assay were used to determine the mycobacterial load in matched lung samples of a murine tuberculosis model. Mice were treated for 24 weeks with 4 treatment arms: isoniazid (H) - rifampicin (R) - pyrazinamide (Z), HRZ-Streptomycin (S), HRZ - ethambutol (E) or ZES.Inverse relationships were observed when comparing TPP with CFU or MBL. Positive associations were observed when comparing CFU with MBL. Description of the net elimination of bacteria was performed for CFU vs. time, MBL vs. time and 1/TTP vs. time and fitted by nonlinear regression. CFU vs. time and 1/TTP vs. time showed bi-phasic declines with the exception of HRZE. A similar rank order, based on the alpha slope, was found comparing CFU vs. time and TTP vs. time, respectively HRZE, HRZ, HRZS and ZES. In contrast, MBL vs. time showed a mono-phasic decline with a flat gradient of elimination and a different rank order respectively, ZES, HRZ, HRZE and HRZS. The correlations found between methods reflects the ability of each to discern the general mycobacterial load. Based on the description of net elimination, we conclude that the MBL assay can detect a subpopulation of Mycobacterium tuberculosis which is not detected by the CFU or TIP assays. (C) 2017 The Authors. Published by Elsevier Ltd.