NEJM：药物利奈唑胺或可治疗广泛的耐药性结核病

刊登在国际著名杂志NEJM上的一项研究结果揭示了，药物利奈唑胺（linezolid）对于治疗广谱耐药性的结核病（TDR-TB）表现出了明显的疗效，而且很少有病人产生耐药性。该药物是治疗急性细菌感染的有效药物。然而接受该药物治疗的病人有82%都表现出了明显的不良事件，可能是由于服用药物的关系。

XDR-TB是一种至少对当前4种治疗肺结核的药物产生耐药的一种肺结核疾病，尽管该类疾病非常罕见，但是世界上77个国家在2011年报道其国家至少出现过一例病症。

来自国立卫生研究院等处的研究者对韩国两所医院的慢性XDR-TB患者进行了相关的研究，这些病人在6个月的治疗过程中对任何疗法都无反应。患者中，72%的为年龄在20至64岁的男性，其中病人随机进行服药，19人日服用利奈唑胺600毫克（快速进行小组），而另外20人在两个月之后服用利奈唑胺（延迟小组）。参与者随机进行长达18个月日服用剂量600mg或者300mg的测试，而且病人随时进行监测以免发生严重的不良反应。

4个月后，快速进行小组19人中有15人，延迟小组20人中有7人不再进行TB的阳性测试，在利奈唑胺6个月治疗后，87%的患者都不再进行阳性的细菌谱测试了。

这项研究中，31位患者经历了临床上明显的不良事件，这或许和药物的使用有关，其中仅仅有3人因为严重的副作用而中断了药物的服用。最终13人完成了试验，在治疗后的12个月内并没有旧病复发。

研究者总结道，利奈唑胺或许在未来会成为治疗XDR-TB的一个潜在治疗选择，而且其可以形成一种治疗MDR-TB的治疗体系，于此同时，额外的临床试验也需要进行来鉴别合适的服药剂量。

与结核相关的拓展阅读：

• ACIE：化学半合成法发现抗结核新型化合物
• ERJ：QFT-MT可有效诊断儿童结核病
• Lancet Infect Dis：大型Meta分析显示激素治疗结核获益
• 中国学生成结核病易感人群
• 《结核病防治管理办法》修订将于2013年3月24日起实施 更多信息请点击：有关结核更多资讯

Linezolid for Treatment of Chronic Extensively Drug-Resistant Tuberculosis

Myungsun Lee, M.D., Jongseok Lee, Ph.D., Matthew W. Carroll, M.D., Hongjo Choi, M.D., Seonyeong Min, R.N., Taeksun Song, Ph.D., Laura E. Via, Ph.D., Lisa C. Goldfeder, C.C.R.P., Eunhwa Kang, M.Sc., Boyoung Jin, R.N., Hyeeun Park, R.N., Hyunkyung Kwak, B.S., Hyunchul Kim, Ph.D., Han-Seung Jeon, M.S., Ina Jeong, M.D., Joon Sung Joh, M.D., Ray Y. Chen, M.D., Kenneth N. Olivier, M.D., Pamela A. Shaw, Ph.D., Dean Follmann, Ph.D., Sun Dae Song, M.D., Ph.D., Jong-Koo Lee, M.D., Dukhyoung Lee, M.D., Cheon Tae Kim, M.D., Veronique Dartois, Ph.D., Seung-Kyu Park, M.D., Sang-Nae Cho, D.V.M., Ph.D., and Clifton E. Barry, III, Ph.D.

Background Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis. Full Text of Background... Methods We enrolled 41 patients who had sputum-culture–positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring. Full Text of Methods... Results By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P=0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed. Full Text of Results... Conclusions Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.)