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omadacycline治疗社区获得性细菌性肺炎
Omadacycline for Community-Acquired Bacterial Pneumonia


Roman Stets ... 呼吸系统疾病 • 2019.02.07
NEJM 动画解读

omadacycline治疗细菌性肺炎
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omadacycline——治疗成人社区获得性肺炎的新药

 

王业明,周飞,谷晓颖,曹彬*

代表中国肺炎研究网(CAP-China)

中日友好医院呼吸与危重症医学科;国家呼吸疾病临床研究中心;中国医学科学院呼吸病学研究院;首都医科大学呼吸病学系感染临床诊疗与研究中心;清华大学-北京大学生命科学联合中心

*通讯作者

 

2019年2月7日,《新英格兰医学杂志》(NEJM)发表了Roman Stets等题为Omadacycline for Community-Acquired Bacterial PneumoniaOPTIC的3期多中心双盲随机对照临床研究1

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摘要


背景

omadacycline是一种可每日1次静脉或口服给药的新型氨甲基环素类(aminomethylcycline)抗生素,在肺组织内可达到高浓度,并对引起社区获得性细菌性肺炎的常见病原体有活性。

 

方法

在一项双盲试验中,我们(以1∶1的比例)将社区获得性细菌性肺炎(肺炎严重指数[Pneumonia Severity Index,PSI]风险分级为II、III或IV级)成人患者随机分组,接受omadacycline(前两剂每12小时静脉给药100 mg,随后每24小时静脉给药100 mg)或莫西沙星(每24小时静脉给药400 mg)治疗。3日后允许分别转为口服omadacycline(每24小时300 mg)或莫西沙星(每24小时400 mg)治疗;总的治疗持续时间为7~14日。主要终点为早期临床缓解,其定义为在未接受挽救性抗菌药治疗的情况下患者生存,四种症状(咳嗽、痰液产生、胸膜炎性胸痛和呼吸困难)中至少两种有改善,并且症状在72~120小时无恶化。次要终点为在最后一次给药后5~10日进行的治疗后评估时,研究者判定的临床缓解,临床缓解的定义为症状或体征消退或改善至不需要进一步抗菌药治疗的程度。使用10个百分点作为非劣效性界值。

 

结果

意向治疗人群包括omadacycline组386例患者和莫西沙星组388例患者。omadacycline的早期临床缓解率不劣于莫西沙星(分别为81.1%和82.7%;差异,-1.6个百分点;95%置信区间[CI],-7.1~3.8),治疗后评估时研究者判定的临床缓解率分别为87.6%和85.1%(差异,2.5个百分点;95% CI,-2.4~7.4)。omadacycline组41.1%的患者和莫西沙星组48.5%的患者报告了治疗开始后发生的不良事件;最常见的事件为胃肠道事件(分别为10.2%和18.0%),两组差异最大的是腹泻发生率(1.0%和8.0%)。试验期间发生了12例死亡(omadacycline组8例和莫西沙星组4例)。

 

结论

用于治疗社区获得性细菌性肺炎成人患者时,omadacycline不劣于莫西沙星(由Paratek制药[Paratek Pharmaceuticals]资助;OPTIC在ClinicalTrials.gov注册号为NCT02531438)。





作者信息

Roman Stets, M.D., Ph.D., Monica Popescu, M.D., Joven R. Gonong, M.D., Ismail Mitha, M.D., William Nseir, M.D., Andrzej Madej, M.D., Ph.D., Courtney Kirsch, B.S., Anita F. Das, Ph.D., Lynne Garrity-Ryan, Ph.D., Judith N. Steenbergen, Ph.D., Amy Manley, B.S., Paul B. Eckburg, M.D., Evan Tzanis, B.S., Paul C. McGovern, M.D., and Evan Loh, M.D.
From City Clinical Hospital #6, Zaporizhzhia, Ukraine (R.S.); Sf. Pantelimon Clinical Emergency Hospital, Bucharest, Romania (M.P.); Lung Center of the Philippines, Manila (J.R.G.); Lakeview Hospital, Benoni, South Africa (I.M.); EMMS, Nazareth Hospital, Nazareth, and Faculty of Medicine in the Galilee, Bar-Ilan University, Safed — both in Israel (W.N.); the Department of Internal Medicine and Pharmacology, Andrzej Frycz Modrzewski Krakow University, Krakow, Poland (A. Madej); AD Stats Consulting, Guerneville, CA (A.F.D.); and Paratek Pharmaceuticals, King of Prussia, PA (C.K., L.G.-R., J.N.S., A. Manley, P.B.E., E.T., P.C.M., E.L.). Address reprint requests to Dr. Garrity-Ryan at Paratek Pharmaceuticals, 1000 First Ave., Suite 200, King of Prussia, PA 19406, or at lynne.garrity-ryan@paratekpharma.com. The investigators in the OPTIC Study are listed in the Supplementary Appendix, available at NEJM.org.

 

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