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成人社区获得性肺炎的抗生素治疗方案
Antibiotic Treatment Strategies for Community-Acquired Pneumonia in Adults


Douwe F. Postma ... 呼吸系统疾病 • 2015.04.02
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成人社区获得性肺炎(CAP)抗生素治疗策略研究

 

曹彬

中日友好医院,中日医院呼吸中心呼吸与危重症医学科

 

社区获得性肺炎(CAP)是世界范围内发病率和病死率最高的疾病之一,尤其对于老年人。约80% CAP患者病情轻,可以安全地门诊治疗,但是仍有20% CAP患者病情严重,需要住院治疗。对于住普通病房、不需要住ICU患者的经验性抗感染治疗,欧美指南都推荐 β内酰胺类抗生素联合大环内酯类1,2;或者单用呼吸氟喹诺酮。由此导致这一类CAP患者大环内酯类和氟喹诺酮的用量增加,加重了耐药风险。但实际上,这种联合抗感染治疗推荐意见的循证医学证据来自回顾性病例总结,证据是不充分的。《新英格兰医学杂志》在2015年4月2日发表了一项荷兰于2011~2013年完成的CAP抗生素药物干预的前瞻性、多中心、随机分组交叉试验,结果显示:以90天病死率作为主要评价指标,对于住普通病房、不需要住ICU的成人CAP患者, β内酰胺类抗生素单药治疗组与 β内酰胺类抗生素联合大环内酯类组,以及呼吸氟喹诺酮治疗组疗效相同3。该研究表明:住普通病房、不需要住ICU的成人CAP, β内酰胺类抗生素经验性治疗同样有效。

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摘要


背景

对于收入非重症监护病房(ICU)的临床疑似社区获得性肺炎(CAP)患者,因证据有限,所以经验性抗生素治疗的选择较为复杂。我们比较了β-内酰胺单药疗法、β-内酰胺-大环内酯联合疗法和氟喹诺酮单药疗法的经验性治疗(允许医学因素对方案的偏离)方案。

 

方法

在4个月期间使用轮换方案的一项集群随机交叉试验中,我们在意向治疗分析中采用3个百分点的非劣效性边界和双侧90%置信区间[CI],检验了β-内酰胺方案与β-内酰胺-大环内酯和氟喹诺酮两种方案相比在90日死亡率方面的非劣效性。

 

结果

共纳入患者数量在β-内酰胺方案期间为656例、β-内酰胺-大环内酯方案期间为739例、氟喹诺酮方案期间为888例,方案依从率分别为93.0%、88.0%、92.7%。患者中位年龄为70岁。在这些治疗方案期间,90日粗死亡率分别为9.0%(59例)、11.1%(82例)和8.8%(78例)。在意向治疗分析中,死亡危险在β-内酰胺-大环内酯方案中比β-内酰胺方案中增高了1.9个百分点(90% CI,-0.6~4.4),而在氟喹诺酮方案中比β-内酰胺方案中降低了0.6个百分点(90% CI,-2.8~1.9)。这些结果表明了β-内酰胺方案的非劣效性。所有治疗方案的住院中位时间为6日,开始口服治疗的中位时间在氟喹诺酮方案中为3日(四分位距,0~4日),在其他方案中为4日(四分位距,3~5日)。

 

结论

在临床疑似CAP而被收入非ICU病房的患者中,以β-内酰胺单药疗法作为首选经验性治疗方案,在90日死亡率方面不劣于β-内酰胺-大环内酯联合或氟喹诺酮单药疗法(由荷兰卫生研究与发展组织[Netherlands Organization for Health Research and Development]资助;CAP-START在ClinicalTrials.gov注册号为NCT01660204)。





作者信息

Douwe F. Postma, M.D., Cornelis H. van Werkhoven, M.D., Leontine J.R. van Elden, M.D., Ph.D., Steven F.T. Thijsen, M.D., Ph.D., Andy I.M. Hoepelman, M.D., Ph.D., Jan A.J.W. Kluytmans, M.D., Ph.D., Wim G. Boersma, M.D., Ph.D., Clara J. Compaijen, M.D., Eva van der Wall, M.D., Jan M. Prins, M.D., Ph.D., Jan J. Oosterheert, M.D., Ph.D., and Marc J.M. Bonten, M.D., Ph.D., for the CAP-START Study Group*
From the Julius Center for Health Sciences and Primary Care (D.F.P., C.H.W., M.J.M.B.) and the Departments of Internal Medicine and Infectious Diseases (D.F.P., A.I.M.H., J.J.O.) and Medical Microbiology (M.J.M.B.), University Medical Center Utrecht, and the Departments of Internal Medicine (D.F.P.), Pulmonology (L.J.R.E.), and Medical Microbiology (S.F.T.T.), Diakonessenhuis Utrecht, Utrecht, the Department of Medical Microbiology, Amphia Ziekenhuis Breda, Breda (J.A.J.W.K.), the Department of Pulmonology, Medisch Centrum Alkmaar, Alkmaar (W.G.B.), the Department of Internal Medicine, Kennemer Gasthuis Haarlem, Haarlem (C.J.C.), the Department of Pulmonology, Spaarne Ziekenhuis, Hoofddorp (E.W.), and the Department of Internal Medicine, Academic Medical Center Amsterdam, Amsterdam (J.M.P.) — all in the Netherlands.Address reprint requests to Dr. van Werkhoven at the University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, P.O. Box 85500, 3508 GA Utrecht, the Netherlands, or at c.h.vanwerkhoven@umcutrecht.nl. *A complete list of investigators in the Community-Acquired Pneumonia — Study on the Initial Treatment with Antibiotics of Lower Respiratory Tract Infections (CAP-START) Study Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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