Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis
Standardised shorter regimens versus individualised longer regimens for rifampin- or multidrug-resistant tuberculosis
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DOI：
10.1183/13993003.01467-2019
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发表时间：
2020-03-01
影响因子：
24.3
通讯作者：
Khan, Faiz Ahmad
中科院分区：
文献类型：
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作者：
Abidi, Syed;Achar, Jay;Khan, Faiz Ahmad
我们试图比较世界卫生组织（WHO）推荐的两种治疗利福平或多药耐药（RR/MDR）结核病（TB）的方案的有效性：9-12个月的标准化方案（“较短方案”）和>= 20个月的个体化方案我们从通过系统评价和公开征集数据确定的观察性研究中收集了个体患者数据。我们纳入了符合WHO资格标准的较短方案患者：既往未接受过二线药物治疗，以及氟喹诺酮类和二线注射剂敏感的RR/MDR-TB。我们使用倾向评分匹配、混合效应荟萃回归来计算失败或复发的调整后比值比和调整后风险差异（aRD），治疗开始后12个月内死亡，失访。我们纳入了3378例中的2625例（77.7%）的个体来自9项较短方案的研究，2717/13104（20.7%）的个体来自53项较长方案的研究。较短治疗方案的治疗成功率高于较长治疗方案（汇总比例为80.0% vs 75.3%），因为前者的失访较少（aRD-0.15，95% CI -0.17-0.12）。总的来说，治疗方案越短，失败或复发的风险差异越高（aRD 0.02，95% CI 0-0.05）和更大的幅度，基线时对吡嗪酰胺耐药（aRD 0.12，95% CI 0.07-0.16），丙硫异烟胺/乙硫异烟胺（aRD 0.07，95% CI -0.01-0.16）或乙胺丁醇（aRD 0.09，95% CI 0.04-0.13）在符合WHO使用标准的患者中，与个体化的较长方案相比，标准化的较短方案与治疗期间的随访损失显著减少相关，并且在存在对组分药物的耐药性的情况下与更多的失败或复发相关。我们的研究结果支持需要改善获得可靠的药物敏感性测试。
We sought to compare the effectiveness of two World Health Organization (WHO)-recommended regimens for the treatment of rifampin- or multidrug-resistant (RR/MDR) tuberculosis (TB): a standardised regimen of 9-12 months (the "shorter regimen") and individualised regimens of >= 20 months ("longer regimens").We collected individual patient data from observational studies identified through systematic reviews and a public call for data. We included patients meeting WHO eligibility criteria for the shorter regimen: not previously treated with second-line drugs, and with fluoroquinolone- and second-line injectable agent-susceptible RR/MDR-TB. We used propensity score matched, mixed effects meta-regression to calculate adjusted odds ratios and adjusted risk differences (aRDs) for failure or relapse, death within 12 months of treatment initiation and loss to follow-up.We included 2625 out of 3378 (77.7%) individuals from nine studies of shorter regimens and 2717 out of 13 104 (20.7%) individuals from 53 studies of longer regimens. Treatment success was higher with the shorter regimen than with longer regimens (pooled proportions 80.0% versus 75.3%), due to less loss to follow-up with the former (aRD -0.15, 95% CI -0.17-0.12). The risk difference for failure or relapse was slightly higher with the shorter regimen overall (aRD 0.02, 95% CI 0-0.05) and greater in magnitude with baseline resistance to pyrazinamide (aRD 0.12, 95% CI 0.07-0.16), prothionamide/ethionamide (aRD 0.07, 95% CI -0.01-0.16) or ethambutol (aRD 0.09, 95% CI 0.04-0.13).In patients meeting WHO criteria for its use, the standardised shorter regimen was associated with substantially less loss to follow-up during treatment compared with individualised longer regimens and with more failure or relapse in the presence of resistance to component medications. Our findings support the need to improve access to reliable drug susceptibility testing.