Hu Yongfeng, Zhang Yan, Ren Xianwen, Liu Yingmei, Xiao Yan, Li Li, Yang Fan, Su Haoxiang, Liu Feng, Liu Haiying, Cao Bin, Jin Qi
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
Department of Infectious Diseases and Clinical Microbiology, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China; Centre of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China; National Clinical Research Centre for Respiratory Disease, Beijing, China.
J Clin Virol. 2016 Mar;76:45-50. doi: 10.1016/j.jcv.2015.12.013. Epub 2016 Jan 4.
Bacterial pneumonia is a well-recognized sequela of patient suffering from influenza, and a key factor, with cytokine dysregulation, that contribute to severe disease and mortality.
To obtain a comprehensive assessment of lung microbial community dynamics in a fatal influenza H7N9 case during the whole clinical course, we undertook a longitudinal study.
Serial bronchoalveolar lavage fluid samples were collected from a H7N9 patient after illness onset, and the microbiome was characterized by using next-generation sequencing and microbiological approaches. Furthermore, the kinetics of circulating cytokine storms related to viral and secondary bacterial infection were analyzed.
Within complex and dynamic communities, the lung microbiome with H7N9 infection were dominated by gram-negative bacteria, Acinetobacter baumannii after the viral invasion and during the whole clinical course. Sputum and blood culture confirmed the secondary bacterial infection with multidrug-resistant A. baumannii 9 days later. The dynamics of the bacterial infection with carbapenem-resistant A. baumannii correlated with antibiotic therapy. Our observations also indicated that sustained high levels of host inflammatory factors, consisting of a set of distinct cytokines associated with disease stage, may contribute to disease progression and death.
This study demonstrates an initial attempt to explore the dynamic microbiome involved inH7N9 infection and its response to antimicrobial therapy, as well as host cytokine response to infection by using next-generation sequencing. These type of investigations with longitudinal follow-up to understand dynamics of microbial community and cytokines involved in lung infection may provide opportunities for development and optimization of targeted antimicrobial therapy and even new therapeutic strategies.
细菌性肺炎是流感患者公认的后遗症，也是导致严重疾病和死亡的关键因素之一，与细胞因子失调有关。
为全面评估1例致命性H7N9流感病例整个临床过程中肺部微生物群落动态变化，我们开展了一项纵向研究。
自1例H7N9患者发病后采集系列支气管肺泡灌洗 fluid样本，采用二代测序和微生物学方法对微生物群进行特征分析。此外，分析了与病毒及继发细菌感染相关的循环细胞因子风暴的动力学变化。
在复杂且动态变化的群落中，H7N9感染患者的肺部微生物群以革兰氏阴性菌为主，病毒入侵后及整个临床过程中鲍曼不动杆菌占主导。9天后痰和血培养证实继发多重耐药鲍曼不动杆菌感染。耐碳青霉烯鲍曼不动杆菌的细菌感染动态变化与抗生素治疗相关。我们的观察还表明，由一组与疾病阶段相关的独特细胞因子组成的宿主炎症因子持续高水平，可能促使疾病进展和死亡。
本研究首次尝试利用二代测序技术探索H7N9感染中涉及的动态微生物群及其对抗菌治疗的反应，以及宿主对感染的细胞因子反应。这类进行纵向随访以了解肺部感染中微生物群落和细胞因子动态变化的研究，可能为开发和优化靶向抗菌治疗乃至新治疗策略提供机会。
