Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study
Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study
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DOI：
10.1016/s0140-6736(12)60734-x
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发表时间：
2012-10-20
期刊：
影响因子：
168.9
通讯作者：
Kang, Hyungseok
中科院分区：
文献类型：
--
作者：
Dalton, Tracy;Cegielski, Peter;Kang, Hyungseok
背景由于多药耐药(MDR)患者二线药物的广泛使用，广泛耐药(XDR)结核病的患病率正在增加。方法从2005年1月1日至2008年12月31日，我们在爱沙尼亚、拉脱维亚、秘鲁、菲律宾、俄罗斯、南非、韩国和泰国招募了连续的在二线治疗开始时确诊为耐多药肺结核的成年人。为了研究目的，药物敏感性测试是在疾病控制和预防中心对11种一线和二线药物进行的集中测试。在1278名患者中，43.7%的患者对至少一种二线药物耐药，20.0%的患者对至少一种二线注射药物耐药，12.9%的患者对至少一种氟喹诺酮类药物耐药。6.7%的患者患有广泛耐药结核病(研究地点的范围为0.8-15.2%)。以前使用二线药物治疗一直是对这些药物产生耐药性的最强风险因素，这会使广泛耐药结核病的风险增加四倍以上。氟喹诺酮耐药和广泛耐药结核病在女性中比男性更常见。失业、酗酒和吸烟与各国对二线注射药物的耐药性有关。其他风险因素因药物和国家不同而不同。解释以前使用二线药物治疗是包括广泛耐药结核病在内的这些药物耐药的强烈、一致的风险因素。具有代表性的药敏结果可指导国内的实验室能力和诊断战略政策。
Background The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries.Methods From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis.Findings Among 1278 patients, 43.7% showed resistance to at least one second-line drug, 20.0% to at least one second-line injectable drug, and 12.9% to at least one fluoroquinolone. 6.7% of patients had XDR tuberculosis (range across study sites 0.8-15.2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries.Interpretation Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies.