Predictors of delayed culture conversion among Ugandan patients
Predictors of delayed culture conversion among Ugandan patients
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DOI：
10.1186/s12879-017-2335-7
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发表时间：
2017-04-24
影响因子：
3.7
通讯作者：
Bonnet, Maryline
中科院分区：
文献类型：
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作者：
Atwine, Daniel;Orikiriza, Patrick;Bonnet, Maryline
背景：在2期试验中，2个月培养转化的估算值可能因培养类型和地理位置不同而不同，非洲地区报告的转化率较低。这项子研究的目的是在6个月的治疗随访期内和跨利福平方案(R10、15和20 mg/kg)比较不同培养基中结核病的检出率，并在乌干达RIFATOX试验点登记的HIV阴性结核病患者中建立2个月培养不转换的预测因素。方法：与其他Rifatox试验点不同，只有在乌干达才使用Lowenstein-Jensen(LJ)和分枝杆菌生长指示管(MGIT)进行治疗监测。在2个月、4个月和6个月时比较不同培养和治疗类型的转化率。结果：在入选的100名患者中，45%的患者在2个月前基于联合LJ和MGIT进行了转换，在不同治疗组之间没有显著差异，p=0.721。在第2个月(58.4%vs 56.0%，p=0.0707)和第4个月(98.9%vs 88.4%，p=0.0391)，LJ的转换率高于MGIT，尤其是在大剂量利福平组。所有患者在6个月前都已康复。MGIT和社会服务岗位上的结核检测时间(TTD)独立预测2个月无转换率。结论：2期临床试验中作为疗效替代指标的2个月培养转换率受用于监测结核分枝杆菌治疗反应的培养方法的影响。因此，使用早期疗效终点的多中心结核病治疗试验应该在不同地点使用相同的培养方法。在接受治疗和从事社会服务工作之前，在MGIT上发现结核分枝杆菌的时间增加了2个月时文化不转换的风险。
Background: Estimates of month-2 culture conversion, a proxy indicator of tuberculosis (TB) treatment efficacy in phase-2 trials can vary by culture-type and geographically with lower rates reported among African sites. The sub-study aimed at comparing TB detection rates of different culture media, within and across rifampicin-based regimens (R10, 15 and 20 mg/Kg) over a 6-month treatment follow-up period, and to establish predictors of month-2 culture non-conversion among HIV-negative TB patients enrolled at RIFATOX trial site in Uganda.Methods: Unlike in other Rifatox Trial sites, it is only in Uganda were Lowenstein-Jensen (LJ) and Mycobacteria growth indicator tube (MGIT) were used throughout 6-months for treatment monitoring. Conversion rates were compared at month-2, 4 and 6 across cultures and treatment-type. Binomial regression analysis performed for predictors of month-2 non-conversion.Results: Of the 100 enrolled patients, 45% had converted based on combined LJ and MGIT by month-2, with no significant differences across treatment arms, p = 0.721. LJ exhibited higher conversion rates than MGIT at month-2 (58.4% vs 56.0%, p = 0.0707) and month-4 (98.9% vs 88.4%, p = 0.0391) respectively, more so within the high-dose rifampicin arms. All patients had converted by month-6. Time-to-TB detection (TTD) on MGIT and social service jobs independently predict month-2 non-conversion.Conclusion: The month-2 culture conversion used in phase 2 clinical trials as surrogate marker of treatment efficacy is influenced by the culture method used for monitoring mycobacterial response to TB treatment. Therefore, multi-centric TB therapeutic trials using early efficacy endpoint should use the same culture method across sites. The Time-to-detection of MTB on MGIT prior to treatment and working in Social service jobs bear an increased risk of culture non-conversion at month-2.