Differentially culturable tubercle bacteria as a measure of tuberculosis treatment response.
Differentially culturable tubercle bacteria as a measure of tuberculosis treatment response.
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DOI：
10.3389/fcimb.2022.1064148
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发表时间：
2022
影响因子：
5.7
通讯作者：
中科院分区：
文献类型：
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结核病新疗法的常规疗效评估包括定量固体培养或常规液体培养，这可能会错过对耐药细菌的定量。为了改进这些评估，需要使用诸如差异可培养结核菌（DCTB）的量化等附加措施进行比较分析。实现这一目标的关键是对结核病治疗反应进行比较测量，使用常规固体和液体培养，液体限制稀释（LLDs）检测痰液中的DCTB。我们招募了treatment-naïve结核患者，有或没有hiv感染，并在治疗过程中连续量化他们的DCTB痰。在治疗前14天对73名患者进行的连续痰取样表明，与常规固体培养相比，DCTB的清除速度较慢。治疗反应表现为四种模式：(1)典型的双相细菌清除；(2)早期无应答者，清除率较慢；(3)开始治疗后细菌数量增加而矛盾恶化；(4)细菌负荷无变化的无应答者。在处理过程中，与定量固体培养相比，LLDs显示出更高的细菌产量。治疗结束后，74%[46/62]的标本显示DCTB残留，该组中有2例复发。治疗结束后的残余DCTB与治疗后两个月MGIT培养、GeneXpert和涂片阳性比例较高相关。无残余DCTB组无复发。这些数据表明，DCTB检测可检测常规固体和液体培养无法检测到的痰液中不同的微生物亚群，并为评估新的结核病治疗方法的疗效提供了重要的替代方法。治疗结束后观察到的残余结核分枝杆菌表明，结核治疗并不总能消除所有细菌群，这一发现应在更大的队列中进行调查。
Routine efficacy assessments of new tuberculosis (TB) treatments include quantitative solid culture or routine liquid culture, which likely miss quantification of drug tolerant bacteria. To improve these assessments, comparative analyses using additional measures such as quantification of differentially culturable tubercle bacteria (DCTB) are required. Essential for enabling this is a comparative measure of TB treatment responses using routine solid and liquid culture with liquid limiting dilutions (LLDs) that detect DCTB in sputum. We recruited treatment-naïve TB patients, with and without HIV-infection, and serially quantified their sputum for DCTB over the course of treatment. Serial sputum sampling in 73 individuals during their first 14 days of treatment demonstrated that clearance of DCTB was slower compared to routine solid culture. Treatment response appeared to be characterized by four patterns: (1) Classic bi-phasic bacterial clearance; (2) early non-responders with slower clearance; (3) paradoxical worsening with an increase in bacterial count upon treatment initiation; and (4) non-responders with no change in bacterial load. During treatment, LLDs displayed greater bacterial yield when compared with quantitative solid culture. Upon treatment completion, 74% [46/62] of specimens displayed residual DCTB and within this group, two recurrences were diagnosed. Residual DCTB upon treatment completion was associated with a higher proportion of MGIT culture, GeneXpert, and smear positivity at two months post treatment. No recurrences occurred in the group without residual DCTB. These data indicate that DCTB assays detect distinct subpopulations of organisms in sputum that are missed by routine solid and liquid culture, and offer important alternatives for efficacy assessments of new TB treatments. The residual DCTB observed upon treatment completion suggests that TB treatment does not always eliminate all bacterial populations, a finding that should be investigated in larger cohorts.
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影响因子：
4.5
作者：
Evangelopoulos D;Shoen CM;Honeyborne I;Clark S;Williams A;Mukamolova GV;Cynamon MH;McHugh TD
通讯作者：
McHugh TD
影响因子：
5.2
作者：
Hu Y;Liu A;Ortega-Muro F;Alameda-Martin L;Mitchison D;Coates A
通讯作者：
Coates A
影响因子：
17.1
作者：
Kamariza M;Shieh P;Ealand CS;Peters JS;Chu B;Rodriguez-Rivera FP;Babu Sait MR;Treuren WV;Martinson N;Kalscheuer R;Kana BD;Bertozzi CR
通讯作者：
Bertozzi CR
DOI：
10.1164/rccm.201604-0769oc
发表时间：
2016-12-15
影响因子：
24.7
作者：
Chengalroyen, Melissa D.;Beukes, Germar M.;Kana, Bavesh D.
通讯作者：
Kana, Bavesh D.
影响因子：
4.6
作者：
Gordhan BG;Peters JS;McIvor A;Machowski EE;Ealand C;Waja Z;Martinson N;Kana BD
通讯作者：
Kana BD