Emmet O'Brien M, Restrepo Marcos I, Martin-Loeches Ignacio
Multidisciplinary Intensive Care Research Organization, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
South Texas Veterans Health Care System, Audie L. Murphy Memorial Veterans Hospital, Medicine, San Antonio, TX, USA.
Respir Investig. 2015 Sep;53(5):201-9. doi: 10.1016/j.resinv.2015.05.003. Epub 2015 Aug 13.
Community-acquired pneumonia (CAP) is a leading cause of death from an infectious cause worldwide. Guideline-concordant antibiotic therapy initiated in a timely manner is associated with improved treatment responses and patient outcomes. In the post-antibiotic era, much of the morbidity and mortality of CAP is as a result of the interaction between bacterial virulence factors and host immune responses. In patients with severe CAP, or who are critically ill, there is a lot of emerging observational evidence demonstrating improved survival rates when treatment using combination therapy with a β-lactam and a macrolide is initiated, as compared to other antibiotic regimes without a macrolide. Macrolides in combination with a β-lactam antibiotic provide broader coverage for the atypical organisms implicated in CAP, and may contribute to antibacterial synergism. However, it has been postulated that the documented immunomodulatory effects of macrolides are the primary mechanism for improved patient outcomes through attenuation of bacterial virulence factors and host systemic inflammatory responses. Despite concerns regarding the limitations of observational evidence and the lack of confirmatory randomized controlled trials, the potential magnitude of mortality benefits estimated at 20-50% cannot be overlooked. In light of recent data from a number of trials showing that combination treatment with a macrolide and a suitable second agent is justified in all patients with severe CAP, such treatment should be obligatory for those admitted to an intensive care setting.
社区获得性肺炎（CAP）是全球感染性疾病致死的主要原因之一。及时启动符合指南的抗生素治疗与改善治疗反应及患者预后相关。在抗生素时代之后，CAP的许多发病率和死亡率是细菌毒力因子与宿主免疫反应相互作用的结果。在重症CAP患者或危重症患者中，有大量新出现的观察性证据表明，与其他不含大环内酯类的抗生素治疗方案相比，启动β-内酰胺类与大环内酯类联合治疗可提高生存率。大环内酯类与β-内酰胺类抗生素联合使用可为CAP中涉及的非典型病原体提供更广泛的覆盖范围，并可能有助于抗菌协同作用。然而，据推测，大环内酯类药物已记录的免疫调节作用是通过减弱细菌毒力因子和宿主全身炎症反应来改善患者预后的主要机制。尽管对观察性证据的局限性以及缺乏确证性随机对照试验存在担忧，但估计死亡率降低20%-50%的潜在幅度不容忽视。鉴于最近多项试验的数据表明，大环内酯类与合适的第二种药物联合治疗对所有重症CAP患者都是合理的，对于入住重症监护病房的患者，这种治疗应成为常规。
