CIBERES, Vall d'Hebron Barcelona Campus Hospital, European Study Group of Infections in Critically Ill Patients (ESGCIP), Barcelona, Spain.
Centre for Experimental Molecular Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Clin Microbiol Infect. 2018 Dec;24(12):1264-1272. doi: 10.1016/j.cmi.2018.03.011. Epub 2018 Mar 24.
Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored.
To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research.
A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed.
The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1).
A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways.
我们目前对脓毒症的病理生理学和治疗方法的理解与临床试验缺乏进展有关,这在一定程度上反映了我们对该综合征异质性的认识不足。因此,应该探索更多针对患者个体的治疗方法。
总结脓毒症精准医学的现有证据,重点是从理论到临床实践的转化。次要目的是制定一个包含管理建议和进一步研究优先事项的框架。
通过 PubMed 搜索引擎在 MEDLINE 数据库中进行了全球搜索策略(最后一次搜索日期为 2017 年 12 月)。未对研究设计、时间或语言进行限制。
本立场文件的重点是治疗方法、病原体和宿主之间的相互作用。关于病原体,讨论了微生物学诊断方法(如血培养(BCs)和快速诊断测试(RDTs))以及靶向抗生素治疗。其他主题包括宿主免疫系统的破坏和脓毒症管理中生物标志物的使用、患者分层和未来临床试验设计。最后,还讨论了个性化抗生素治疗和管理(图 1)。
路线图提供了建议和未来展望。RDTs 和确定药物反应表型是明显的挑战。下一步将基于治疗诊断方法将精准医学应用于脓毒症管理。这种高度个体化的方法对于设计新的临床试验和改善护理途径至关重要。