Zheng Xubin, Zheng Rongrong, Hu Yi, Werngren Jim, Forsman Lina Davies, Mansjö Mikael, Xu Biao, Hoffner Sven
Department of Epidemiology, School of Public Health, Fudan University, and Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, Shanghai, China.
Xiamen Center for Disease Control and Prevention, Fujian Province, China.
Antimicrob Agents Chemother. 2016 Jul 22;60(8):4786-92. doi: 10.1128/AAC.03008-15. Print 2016 Aug.
Our study aims to identify the clinical breakpoints (CBPs) of second-line drugs (SLDs) above which standard therapy fails in order to improve multidrug-resistant tuberculosis (MDR-TB) treatment. MICs of SLDs were determined for M. tuberculosis isolates cultured from 207 MDR-TB patients in a prospective cohort study in China between January 2010 and December 2012. Classification and regression tree (CART) analysis was used to identify the CBPs predictive of treatment outcome. Of the 207 MDR-TB isolates included in the present study, the proportion of isolates above the critical concentration recommended by WHO ranged from 5.3% in pyrazinamide to 62.8% in amikacin. By selecting pyrazinamide as the primary node (CBP, 18.75 mg/liter), 72.1% of sputum culture conversions at month four could be predicted. As for treatment outcome, pyrazinamide (CBP, 37.5 mg/liter) was selected as the primary node to predict 89% of the treatment success, followed by ofloxacin (CBP, 3 mg/liter), improving the predictive capacity of the primary node by 10.6%. Adjusted by identified confounders, the CART-derived pyrazinamide CBP remained the strongest predictor in the model of treatment outcome. Our findings indicate that the critical breakpoints of some second-line drugs and PZA need to be reconsidered in order to better indicate MDR-TB treatment outcome.
我们的研究旨在确定二线药物（SLD）的临床断点（CBP），超过该断点标准治疗即告失败，以改善耐多药结核病（MDR-TB）的治疗。在2010年1月至2012年12月期间在中国进行的一项前瞻性队列研究中，对从207例MDR-TB患者中培养的结核分枝杆菌分离株测定了SLD的最低抑菌浓度（MIC）。采用分类与回归树（CART）分析来确定预测治疗结果的CBP。在本研究纳入的207株MDR-TB分离株中，高于世界卫生组织推荐的临界浓度的分离株比例从吡嗪酰胺的5.3%到阿米卡星的62.8%不等。通过选择吡嗪酰胺作为主要节点（CBP，18.75毫克/升），可以预测4个月时72.1%的痰培养转阴情况。至于治疗结果，选择吡嗪酰胺（CBP，37.5毫克/升）作为主要节点来预测89%的治疗成功情况，其次是氧氟沙星（CBP，3毫克/升），主要节点的预测能力提高了10.6%。经确定的混杂因素调整后，CART得出的吡嗪酰胺CBP在治疗结果模型中仍然是最强的预测因素。我们的研究结果表明，需要重新考虑一些二线药物和吡嗪酰胺的临界断点，以便更好地指示MDR-TB的治疗结果。
