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印度北部时间至阳性和循环阈值(CT)值在预测结核病结局及耐多药方面的预后价值:一项使用液体培养和分子诊断的研究

Prognostic Value of Time-to-Positivity and Cycle Threshold (CT) Values in Predicting Tuberculosis Outcomes and Multidrug Resistance in Northern India: A Study Using Liquid Culture and Molecular Diagnostics.

作者信息

Bir Raunak, Singh Urvashi B, Gautam Hitender, Verma Nishant, Bala Kiran, Mohan Anant, Guleria Randeep

机构信息

Department of Microbiology, Employees' State Insurance Corporation (ESIC) Medical College and Hospital, Faridabad, IND.

Department of Microbiology, All India Institute of Medical Sciences, New Delhi, IND.

出版信息

Cureus. 2025 Jun 15;17(6):e86087. doi: 10.7759/cureus.86087. eCollection 2025 Jun.


DOI:10.7759/cureus.86087
PMID:40672039
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12263343/
Abstract

BACKGROUND: Relapse and default cases of pulmonary tuberculosis (PTB) present a significant challenge due to higher bacillary loads and the increased risk of developing multidrug-resistant tuberculosis (MDR-TB). Conventional diagnostic methods, such as smear microscopy, lack sensitivity and timeliness. This study evaluates the prognostic value of time to positivity (TTP) from liquid culture and cycle threshold (CT) values from GeneXpert /rifampicin (Cepheid, Sunnyvale, CA) in predicting treatment outcomes. OBJECTIVES: This study aimed to assess the utility of baseline mycobacteria growth indicator tube (MGIT) TTP and GeneXpert CTvalues as early biomarkers for prognosis and the risk of MDR-TB development in smear-positive relapse and default PTB patients. METHODS: This cross-sectional study with a prospective arm enrolled 72 adult PTB patients (relapse, default, or treatment failure). Sputum samples underwent smear microscopy, MGIT liquid culture, and GeneXpert testing. Baseline and three-month follow-up results were compared. TTP and CT values were correlated with microbiological outcomes. RESULTS: MGIT culture was positive in 52.8% (38/72) of patients (mean TTP: 26.5 days). In comparison, GeneXpert detected in 70.8% (51/72) (mean CT: 24.4). At follow-up, 7.8% (3/38) remained culture-positive (mean TTP: 29.7 days); one isolate was MDR. Patients with follow-up culture positivity had significantly lower baseline TTP (19.7 ± 3.4 vs. 25.8 ± 3.8 days). CT values trended lower among poor responders but did not reach statistical significance. Logistic regression suggested that a TTP threshold of ≤20.89 days might predict poor outcomes (model accuracy: 70%). CONCLUSION: Baseline MGIT TTP demonstrates significant prognostic potential in identifying patients with PTB at risk of treatment failure or MDR development. In contrast, GeneXpert CT values, while useful diagnostically, were less predictive of outcomes. Incorporating TTP into routine clinical practice could enable earlier intervention and improve TB control strategies in high-burden settings.

摘要

背景:肺结核(PTB)的复发和失访病例带来了重大挑战,因为其细菌载量更高,且发生耐多药结核病(MDR-TB)的风险增加。传统诊断方法,如涂片显微镜检查,缺乏敏感性和及时性。本研究评估液体培养的阳性时间(TTP)和GeneXpert/利福平(Cepheid公司,加利福尼亚州桑尼维尔)的循环阈值(CT)值在预测治疗结果方面的预后价值。 目的:本研究旨在评估基线分枝杆菌生长指示管(MGIT)TTP和GeneXpert CT值作为涂片阳性复发和失访PTB患者预后及MDR-TB发生风险的早期生物标志物的效用。 方法:这项具有前瞻性队列的横断面研究纳入了72例成年PTB患者(复发、失访或治疗失败)。对痰液样本进行涂片显微镜检查、MGIT液体培养和GeneXpert检测。比较基线和三个月随访结果。TTP和CT值与微生物学结果相关。 结果:52.8%(38/72)的患者MGIT培养呈阳性(平均TTP:26.5天)。相比之下,GeneXpert检测到70.8%(51/72)呈阳性(平均CT:24.4)。在随访时,7.8%(3/38)仍培养阳性(平均TTP:29.7天);一株分离菌为耐多药菌。随访培养阳性的患者基线TTP显著更低(19.7±3.4天对25.8±3.8天)。反应不佳者的CT值呈下降趋势,但未达到统计学显著性。逻辑回归表明,TTP阈值≤20.89天可能预测不良结果(模型准确性:70%)。 结论:基线MGIT TTP在识别有治疗失败或耐多药风险的PTB患者方面显示出显著的预后潜力。相比之下,GeneXpert CT值虽然在诊断上有用,但对结果的预测性较差。将TTP纳入常规临床实践可以实现更早的干预,并改善高负担地区的结核病控制策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e235/12263343/a437e5569517/cureus-0017-00000086087-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e235/12263343/a437e5569517/cureus-0017-00000086087-i01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e235/12263343/a437e5569517/cureus-0017-00000086087-i01.jpg

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本文引用的文献

[1]
The Xpert® MTB/RIF cycle threshold value predicts M. tuberculosis transmission to close contacts in a Brazilian prospective multicenter cohort.

Clin Infect Dis. 2024-1-3

[2]
The Interaction of Diabetes and Tuberculosis: Translating Research to Policy and Practice.

Trop Med Infect Dis. 2021-1-8

[3]
Management of drug-resistant tuberculosis.

Lancet. 2019-9-14

[4]
Surveillance of Tuberculosis in Taipei: The Influence of Nontuberculous Mycobacteria.

PLoS One. 2015-11-6

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Lancet Respir Med. 2015-3-9

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N Engl J Med. 2014-10-23

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Time to positivity in liquid culture predicts colony forming unit counts of Mycobacterium tuberculosis in sputum specimens.

Tuberculosis (Edinb). 2013-12-18

[8]
The impact of diabetes on tuberculosis treatment outcomes: a systematic review.

BMC Med. 2011-7-1

[9]
Evaluation of the Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in a high HIV prevalence setting.

Am J Respir Crit Care Med. 2011-4-14

[10]
Laboratory diagnosis of tuberculosis in resource-poor countries: challenges and opportunities.

Clin Microbiol Rev. 2011-4

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