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

阳性时间和循环阈值(CT)值在预测印度北部结核病预后和多重耐药性中的预后价值:一项采用液体培养和分子诊断的研究

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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 Mycobacterium tuberculosis/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 M. tuberculosis 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.

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