Pyrazinamide May Improve Fluoroquinolone-Based Treatment of Multidrug-Resistant Tuberculosis
Pyrazinamide May Improve Fluoroquinolone-Based Treatment of Multidrug-Resistant Tuberculosis
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DOI：
10.1128/aac.01300-12
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发表时间：
2012-11-01
影响因子：
4.9
通讯作者：
Zhang, Ying
中科院分区：
文献类型：
--
作者：
Chang, Kwok-Chiu;Leung, Chi-Chiu;Zhang, Ying
吡嗪酰胺在目前治疗耐多药（MDR）结核病（TB）中的作用尚不确定。从1995年至2009年诊断的耐多药结核病例的全港性登记中，我们收集了194例接受含氟喹诺酮类药物治疗的耐多药肺结核患者。按吡嗪酰胺使用和敏感性分层，有83名吡嗪酰胺敏感性MDR-TB使用者（亚组A），24名吡嗪酰胺耐药MDR-TB使用者（亚组B），40名吡嗪酰胺敏感性MDR-TB非使用者（亚组C），47名吡嗪酰胺耐药MDR-TB非使用者（亚组D）。我们估计了治疗后90天内发生的早期痰培养转换（ARR-培养）和治疗后2年内发生的治愈或治疗完成（ARR-成功）的校正风险比（ARR），这是由于吡嗪酰胺使用敏感性。与亚组B相比，ARR培养和ARR成功分别为1.38（95%置信区间[CI]，0.89 - 2.12）和1.38（95%置信区间[CI]，0.88 - 2.17）。与C亚组相比，相应结果分别为0.99（95% CI，0.81 - 1.22）和0.99（95% CI，0.78 - 1.26），与D亚组相比，相应结果分别为1.09（95% CI，0.84 - 1.42）和0.94（95% CI，0.74 - 1.20）。早期培养转换显著增加治愈或治疗完成的发生率比例71%（95%CI，26%至133%）。吡嗪酰胺非使用者的选择偏差可能低估了吡嗪酰胺的作用。吡嗪酰胺使用者的比较表明，吡嗪酰胺增加了早期培养转换和治愈或治疗完成的发生率比例，最佳估计为38%。这一变化幅度超过了在异烟肼和利福平中加入吡嗪酰胺导致的药物敏感性结核病2个月培养转化率增加15%至20%。吡嗪酰胺在基于氟喹诺酮类药物的耐多药结核病治疗中可能很重要。
The role of pyrazinamide in the current treatment of multidrug-resistant (MDR) tuberculosis (TB) is uncertain. From a territory-wide registry of MDR-TB cases diagnosed between 1995 and 2009, we assembled a cohort of 194 patients with MDR pulmonary TB given fluoroquinolone-containing regimens. Stratified by pyrazinamide use and susceptibility, there were 83 users with pyrazinamide-susceptible MDR-TB (subgroup A), 24 users with pyrazinamide-resistant MDR-TB (subgroup B), 40 nonusers with pyrazinamide-susceptible MDR-TB (subgroup C), and 47 nonusers with pyrazinamide-resistant MDR-TB (subgroup D). We estimated the adjusted risk ratio (ARR) of early sputum culture conversion (ARR-culture) that occurred within 90 days posttreatment and that of cure or treatment completion (ARR-success) that occurred by 2 years posttreatment due to pyrazinamide use with susceptibility. In comparison with subgroup B, ARR-culture and ARR-success were 1.38 (95% confidence interval [CI], 0.89 to 2.12) and 1.38 (95% confidence interval [CI], 0.88 to 2.17), respectively. Corresponding findings were 0.99 (95% CI, 0.81 to 1.22) and 0.99 (95% CI, 0.78 to 1.26) in comparison with subgroup C and 1.09 (95% CI, 0.84 to 1.42) and 0.94 (95% CI, 0.74 to 1.20) in comparison with subgroup D. Early culture conversion significantly increased the incidence proportion of cure or treatment completion by 71% (95% CI, 26% to 133%). Selection bias among pyrazinamide nonusers might have underestimated the role of pyrazinamide. Comparison of pyrazinamide users showed that pyrazinamide increased the incidence proportion of early culture conversion and that of cure or treatment completion by a best estimate of 38% for both. This magnitude of change exceeded the 15 to 20% increase in the 2-month culture conversion rate of drug-susceptible TB that results from adding pyrazinamide to isoniazid and rifampin. Pyrazinamide is likely important in fluoroquinolone-based treatment of MDR-TB.