DETECTIVE: Dissemination and resistance mechanisms of carbapenem-resistant Gram-negative bacilli

现代基因组技术和基因组分析工具的发展已经成功地应用于提高我们对临床上重要的耐多药细菌的出现、传播、短期进化和传播的理解。基因组分析使我们能够以精细的分辨率确定医院间患者转移在国内和国际MDR病原体传播中所起的作用。它使我们能够确定驱动医院和患者内部MDR病原体演变的选择性力量，以及这可能施加的临床影响。基因组分析还被用于确定暴发、潜在暴发来源，并为成功的干预措施提供信息，以结束医院内的暴发。中国医院多药耐药问题的规模正在达到令人震惊的水平。进入21世纪，中国耐多药感染的发病率和死亡率呈逐年上升趋势。最令人担忧的是，由鲍曼不动杆菌、大肠杆菌和肺炎克雷伯菌引起的感染发病率上升，这些细菌对碳青霉烯类抗生素耐药，这是治疗多药耐药病原体感染的最后一种抗生素。中国(www.chinets.com)34家哨所医院的全国CHINET临床微生物学实验室网络报告称，2017年，从临床标本中检出的细菌前三位是大肠埃希菌、肺炎克雷伯菌和鲍曼不动杆菌。已知的耐碳青霉烯类鲍曼不动杆菌13 337例(69.3%)，耐碳青霉烯类肺炎克雷伯菌6434例(23%)，耐碳青霉烯类大肠埃希菌845例(2.3%)。因此，立即对这些细菌进行基因组水平的调查是至关重要的，以便使西方世界在了解传播、传播和感染控制方面取得突破。该网络拟议的研究将围绕三个独立但相互关联的项目进行：1)调查耐碳青霉烯类肺炎克雷伯菌的宿主和传播途径；2)调查耐碳青霉烯类大肠杆菌的群落携带动态，导致菌株不断进入医院和随后的感染。3)调查耐碳青霉烯类鲍曼不动杆菌的宿主和传播途径。

Modern genomic technologies and development of genome analysis tools have been successfully applied to improve our understanding of the emergence, spread, short term evolution, and transmission of clinically important MDR bacteria. Genomic analysis has allowed us to determine with fine scale resolution the role played by inter-hospital patient transfer in national and international dissemination of MDR pathogens. It has allowed us to determine the selective forces which drive the evolution of MDR pathogens in the hospital and within patients and the clinical impact this can impose. Genomic analysis has also been used to identify outbreaks, potential sources of outbreaks, and inform successful interventions to bring an end to outbreaks within hospitals. The scale of the MDR problem in Chinese hospitals is reaching alarming levels. The incidence of morbidity and mortality associated with MDR infections in China has grown year-on-year in the 21st century. Most alarming is the rise in the incidence of infections caused by A. baumannii, E. coli and K. pneumoniae which are resistant to carbapenems, that last line of antibiotics available to treat infections with MDR pathogens. The national CHINET network of clinical microbiology laboratories of 34 sentinel hospitals across China (www.chinets.com) report that in 2017, E. coli, K. pneumoniae and A. baumannii were the top three bacterial species recovered from clinical samples. There were 13,337 known cases of carbapenem resistant A. baumannii (69.3% carbapenem resistance prevalence), 6,434 cases of carbapenem resistant K. pneuomoniae (23% carbapenem resistance prevalence), and 845 cases of carbapenem resistant E. coli (2.3% carbapenem resistance prevalence). It is therefore vital that genomic level investigations of these bacteria are implemented in China immediately, to allow the breakthroughs in understanding transmission, spread, and infection control that have been afforded in the Western world.The proposed research to be conducted by the network will be organised around three independent but inter-connected projects:1) Investigate the reservoirs and routes of transmission of carbapenem resistant K. pneumoniae 2) Investigate the community carriage dynamics of carbapenem resistant E. coli leading to the continuous introduction of strains into hospitals and subsequent infections.3) Investigate the reservoirs and routes of transmission of carbapenem resistant Acinetobacter baumannii.