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含或不含莫西沙星的4个月利福喷丁方案治疗结核病
Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis


Susan E. Dorman ... 呼吸系统疾病 • 2021.05.06
相关阅读
• 突破结核治疗的6个月关卡 • 利福平用药4个月或异烟肼用药9个月治疗成人潜伏性结核 • 利福平耐药结核的短疗程方案试验 • 利用DNA测序预测对一线结核药物的敏感性

摘要


背景

含利福喷丁方案具有很强的抗分枝杆菌活性,因此我们也许可以缩短药物敏感性肺结核患者的疗程。

 

方法

在对13个国家的新诊断肺结核患者开展的开放标签、3期、随机、对照试验中,我们采用6.6个百分点的非劣效性界值比较了两种4个月含利福喷丁方案和标准6个月方案(包括利福平、异烟肼、吡嗪酰胺和乙胺丁醇)(对照)。在一种4个月方案中,利福平被利福喷丁取代;在另一种方案中,利福平被利福喷丁取代,而乙胺丁醇被莫西沙星取代。主要疗效结局是12个月时的无结核病生存。

 

结果

在接受随机分组的2,516例参与者中,2,343例的培养结果显示对异烟肼、利福平或氟喹诺酮类不耐药的结核分枝杆菌阳性(符合微生物学标准的人群;对照组768例,利福喷丁-莫西沙星组791例,利福喷丁组784例),其中194例合并感染人类免疫缺陷病毒(HIV),1,703例的胸片可见空洞形成。共计2,234例参与者的主要结局可评估(可评估的人群;对照组726例,利福喷丁-莫西沙星组756例,利福喷丁组752例)。在符合微生物学标准的人群(15.5% vs. 14.6%有不良结局;差异,1.0个百分点;95%置信区间[CI],-2.6~4.5)和可评估的人群(11.6% vs. 9.6%;差异,2.0个百分点;95% CI,-1.1~5.1)中,利福喷丁+莫西沙星均不劣于对照。次要和敏感性分析也证明了非劣效性。在任一人群中,不含莫西沙星的利福喷丁方案均未被证明不劣于对照(在符合微生物学标准的人群中,17.7% vs. 14.6%有不良结局;差异,3.0个百分点[95% CI,-0.6~6.6];在可评估的人群中,14.2% vs. 9.6%;差异,4.4个百分点[95% CI,1.2~7.7])。在治疗期间,对照组19.3%的参与者、利福喷丁-莫西沙星组18.8%的参与者和利福喷丁组14.3%的参与者发生了3级或更高级别的不良事件。

 

结论

在结核病治疗中,含莫西沙星的4个月利福喷丁方案不劣于标准6个月方案(由美国疾病控制与预防中心等资助,研究31/A5349在ClinicalTrials.gov注册号为NCT02410772)。





作者信息

Susan E. Dorman, M.D., Payam Nahid, M.D., M.P.H., Ekaterina V. Kurbatova, M.D., Ph.D., M.P.H., Patrick P.J. Phillips, Ph.D., Kia Bryant, M.P.H., Kelly E. Dooley, M.D., Ph.D., Melissa Engle, C.R.T., C.C.R.C., Stefan V. Goldberg, M.D., Ha T.T. Phan, Dr.P.H., M.D., James Hakim, M.D., John L. Johnson, M.D., Madeleine Lourens, M.B., Ch.B., Ph.D., Neil A. Martinson, M.B., B.Ch., M.P.H., Grace Muzanyi, M.B., Ch.B., Kim Narunsky, M.B., Ch.B., Sandy Nerette, M.D., Nhung V. Nguyen, M.D., Ph.D., Thuong H. Pham, M.D., M.P.H., Samuel Pierre, M.D., Anne E. Purfield, Ph.D., Wadzanai Samaneka, M.B., Ch.B., Radojka M. Savic, Ph.D., Ian Sanne, M.B., B.Ch., D.T.M.H., Nigel A. Scott, M.S., Justin Shenje, M.B., Ch.B., Erin Sizemore, M.P.H., Andrew Vernon, M.D., M.H.S., Ziyaad Waja, M.B., B.Ch., M.P.H., Marc Weiner, M.D., Susan Swindells, M.B., B.S., and Richard E. Chaisson, M.D. for the AIDS Clinical Trials Group and the Tuberculosis Trials Consortium
From the Medical University of South Carolina, Charleston (S.E.D.); the UCSF Center for Tuberculosis, University of California, San Francisco, San Francisco (P.N., P.P.J.P., R.M.S.); the Vietnam National Tuberculosis Program–University of California, San Francisco Research Collaboration Unit (P.N., P.P.J.P., H.T.T.P., N.V.N., T.H.P., R.M.S.) and the National Lung Hospital (N.V.N., T.H.P.) — both in Hanoi; the Centers for Disease Control and Prevention, Atlanta (E.V.K., K.B., S.V.G., A.E.P., N.A.S., E.S., A.V.); the University of Texas Health Science Center at San Antonio and the South Texas Veterans Health Care System, San Antonio (M.E., M.W.); the University of Zimbabwe College of Health Sciences, Harare (J.H., W.S.); Case Western Reserve University, University Hospitals Cleveland Medical Center, Cleveland (J.L.J.); the Uganda–Case Western Reserve University Research Collaboration, Kampala (J.L.J., G.M.); TASK (M.L.), the University of Cape Town Lung Institute (K.N.), and the South African Tuberculosis Vaccine Initiative (J.S.), Cape Town, the Perinatal HIV Research Unit, University of the Witwatersrand (N.A.M., Z.W.), and the Wits Health Consortium (I.S.), Johannesburg — all in South Africa; Johns Hopkins University School of Medicine, Baltimore (K.E.D., N.A.M., R.E.C.), and the U.S. Public Health Service Commissioned Corps, Rockville (A.E.P.) — both in Maryland; the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic Infections (GHESKIO), Port-au-Prince (S.N., S.P.); and the University of Nebraska Medical Center, Omaha (S.S.). Address reprint requests to Dr. Nahid at the UCSF Center for Tuberculosis, University of California, San Francisco, 1001 Potrero Ave. 5K1, San Francisco, CA 94110, or at pnahid@ucsf.edu.

 

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