World Health Organization-Country Office for India, New Delhi, India.
National AIDS Control Organization, Ministry of Health and Family Welfare, Government of India, New Delhi, India.
PLoS One. 2018 Apr 11;13(4):e0193903. doi: 10.1371/journal.pone.0193903. eCollection 2018.
Globally, India has the world's highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP.
To evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment.
This is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics.
In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92-125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202-381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed doses in intensive phase (IP) and continuation phase (CP); cavitary disease; prior treatment episodes characterized by re-treatment regimen taken twice, longer duration and more episodes of treatment; any weight loss during treatment; males and additional resistance to first line drugs (Ethambutol, Streptomycin). In a subgroup of 104 MDR-TB patients, 62 (59.6%) had Ofloxacin resistance among whom only 25.8% had treatment success, half of the success (54.8%) seen in Ofloxacin sensitive patients. Baseline susceptibility to Ofloxacin (HR 2.04) and Kanamycin (HR 4.55) significantly doubled and quadrupled the chances for culture conversion respectively while baseline susceptibility to Ofloxacin (AOR 0.37) also significantly reduced the odds of unfavorable treatment outcomes (p value ≤0.05) in multinomial logistic regression model.
India's initial MDR-TB patients' cohort treated under the RNTCP experienced poor treatment outcomes. To address the factors associated with poor treatment outcomes revealed in our study, a systematic multi-pronged approach would be needed. A series of policies and interventions have been developed to address these factors to improve DR-TB treatment outcomes and are being scaled-up in India.
在全球范围内，印度拥有世界上最高的耐多药结核病（MDR-TB）负担。印度的 Programmatic Management of Drug Resistant TB（PMDT）于 2007 年开始，2013 年初实现全国覆盖。修订后的国家结核病控制规划（RNTCP）下最初的微生物学结果不佳促使进行了详细分析。这是第一项关于与 RNTCP 下治疗的 MDR-TB 患者不良结局显著相关的因素的研究。
评估 2007 年至 2011 年初在印度注册的 MDR-TB 患者的初始痰培养转换、培养逆转和最终治疗结局，这些患者接受了标准的 24 个月方案，每日观察治疗。
这是一项回顾性队列研究。从 PMDT 记录中提取临床和微生物学数据。初始痰培养转换、培养逆转和治疗结局按照国家对世卫组织标准定义（2008 年）的适应性进行定义。使用 Cox 比例风险模型进行逻辑回归、多项逻辑回归和调整后的优势比，以评估与中期和最终结局相关的因素，同时控制人口统计学和临床特征。
在 3712 例 MDR-TB 患者的队列中，2735 例（73.6%）在 100 天的中位数（92-125）时有初始痰培养转换，其中 506 例（18.5%）在 279 天的中位数（202-381）时有培养逆转。2264 例患者的治疗结局可用，而 1448 例（39.0%）患者仍在治疗中或在分析时尚未确定结局。在 2264 例患者中，781 例（34.5%）治疗成功，644 例（28.4%）死亡，670 例（29.6%）失访，169 例（7.5%）治疗失败或转为广泛耐药结核病治疗。与培养不转换、培养逆转和/或不良治疗结局显著相关的因素是基线 BMI<18；强化期（IP）和持续期（CP）错过≥7 次剂量；空洞性疾病；以前的治疗阶段特征为采用双重再治疗方案、治疗时间更长、治疗次数更多；治疗期间任何体重减轻；男性和一线药物（乙胺丁醇、链霉素）的额外耐药性。在 104 例 MDR-TB 患者的亚组中，有 62 例（59.6%）对氧氟沙星耐药，其中只有 25.8%治疗成功，而氧氟沙星敏感患者中有一半（54.8%）治疗成功。基线对氧氟沙星（HR 2.04）和卡那霉素（HR 4.55）的敏感性分别显著增加了 2 倍和 4 倍，使培养转换的可能性分别增加了 2 倍和 4 倍，而基线对氧氟沙星的敏感性（AOR 0.37）也显著降低了不利治疗结局的几率（p 值≤0.05）在多项逻辑回归模型中。
印度 RNTCP 下治疗的初始 MDR-TB 患者队列经历了不良的治疗结局。为了解决我们研究中发现的与不良治疗结局相关的因素，需要采取系统的多方面方法。为了解决这些因素，印度制定了一系列政策和干预措施来改善耐多药结核病的治疗结局，并正在扩大规模。
