重症烧伤病房鲍曼不动杆菌的分子流行病学研究
发布时间：2018-08-22 08:01
【摘要】：鲍曼不动杆菌(Acinetobacter baumannii)是医院常见的条件致病菌,与重症患者的感染密切相关,常引起呼吸机相关性肺炎、尿路感染、败血症、创口感染及中枢神经系统感染等。鲍曼不动杆菌营养要求低,极易在医院环境的物体表面存活和传播,从而导致医院感染的暴发流行。Pubmed最新的数据显示,克隆复合体92(Clonal complex 92,CC92)遍布了亚洲、欧洲、美洲、澳洲等多个国家以及中国的大部分地区,是全球流行最为广泛的克隆复合体。除此之外,鲍曼不动杆菌的耐药问题也不容忽视,抗生素的广泛运用及耐药基因容易在不同鲍曼不动杆菌之间水平传播使得耐药率不断增加。重症烧伤患者大面积皮肤缺损、介入性操作、广谱抗生素的广泛运用以及重症烧伤患者免疫力低下等因素都为鲍曼不动杆菌的入侵提供了良好的机会。在2011-2012年期间,我们对第三军医大学第一附属医院烧伤科重症患者临床微生物样本的菌株分离和耐药情况进行了研究,结果显示重症患者鲍曼不动杆菌分离率高达34.4%,对碳青霉烯类抗生素耐药率高达89.5%。随后,我们对重症病房环境中的鲍曼不动杆菌进行了筛查,在患者的床单元、心电监护仪按钮、输液泵按钮以及医护人员的手上均分离出了鲍曼不动杆菌。然而,患者临床微生物样本中的鲍曼不动杆菌和病房环境中的鲍曼不动杆菌之间是否有相关性?为何耐药率如此之高?这些问题都是一个未知数。本研究主要围绕这两个问题展开。本研究通过脉冲场电泳(Pulsed-field gel electrophoresis,PFGE)和多位点序列分析(Multi-locus sequence typing,MLST)两种技术对重症烧伤患者临床微生物样本及病房环境样本中分离的鲍曼不动杆菌进行基因分型。结果显示,PFGE以G、F、I、H这四个型别为主,MLST以ST368、ST369、ST195和ST191为主,两种不同分型方法的主要型别中均有患者和病房环境样本的检出。除了基因分型以外,我们还对这两种不同来源菌株的β-内酰胺类抗生素耐药机制进行了初探,其中包括鲍曼不动杆菌最常见的β-内酰胺酶耐药基因和最为复杂的外排泵机制。β-内酰胺酶耐药基因检测结果显示,无论是患者样本还是病房样本,A类的bla PER、B类的blaVIM、C类的blaAmp C和D类的blaOXA-23均有较高的检出率,其中D类的blaOXA-51检出率100%。鲍曼不动杆菌的外排泵中,Ade ABC外排的抗生素在临床上运用最为广泛。同时,adeABC操纵子还受上游二元调控系统AdeR/AdeS的严格调控。该二元调控系统编码基因Ade R/Ade S均出现了碱基的突变且导致了氨基酸的突变,并引起了外排泵基因ade B表达量明显上调,这可能是最终导致鲍曼不动杆菌耐药率普遍升高的原因。
[Abstract]:Acinetobacter baumannii (Acinetobacter baumannii) (Acinetobacter baumannii) is a common opportunistic pathogen in hospitals, which is closely related to the infection of severe patients. It often causes ventilator-associated pneumonia, urinary tract infection, septicemia, wound infection and central nervous system infection. Acinetobacter baumannii has low nutritional requirements and can easily survive and spread on the surface of objects in the hospital environment, resulting in an outbreak of nosocomial infection. Pubmed's latest data show that the clone complex 92 (Clonal complex 92 CC92 is found in Asia, Europe, and America. Australia and other countries, as well as most parts of China, are the most prevalent clone complexes in the world. In addition, the drug resistance of Acinetobacter baumannii can not be ignored. The widespread use of antibiotics and the easy spread of drug resistance genes among different Acinetobacter baumannii make the drug resistance rate increase. The factors such as large area skin defect, interventional operation, extensive use of broad-spectrum antibiotics and low immunity of severe burn patients all provide a good opportunity for the invasion of Acinetobacter baumannii. During the period 2011-2012, we studied the isolation and drug resistance of strains from the clinical microorganism samples of severe patients in the Department of Burns, first affiliated Hospital of the third military Medical University. The results showed that the isolation rate of Acinetobacter baumannii was 34. 4% and the resistance rate to carbapenem antibiotics was 89. 5% in severe patients. We then screened Acinetobacter baumannii in the intensive care unit environment and isolated Acinetobacter baumannii from the patient's bed unit, ECG monitor buttons, infusion pump buttons, and the hands of health care workers. However, is there a correlation between Acinetobacter baumannii in patients' clinical microbial samples and Acinetobacter baumannii in ward settings? Why is the drug resistance rate so high? These problems are an unknown. This study focuses on these two problems. In this study, the genotyping of Acinetobacter baumannii isolated from clinical microorganism samples and environmental samples of patients with severe burn was carried out by Pulsed-field gel electrophoresis-PFGE and Multi-locus sequence typing. The results showed that the four main types of PFGE were Glutathione Igna H and MLST were mainly ST368 / ST369 / ST195 and ST191. The main types of the two different typing methods were patient and ward environment samples. In addition to genotyping, we also studied the mechanism of 尾-lactam antibiotic resistance in these two strains from different sources. These include the most common 尾 -lactamase resistance genes of Acinetobacter baumannii and the most complex efflux pump mechanisms. The detection rates of blaAmp C and blaOXA-23 of bla Perot B and D were higher in both patient samples and ward samples. The detection rate of blaOXA-51 in D group was 100%. In Acinetobacter baumannii efflux pump, Ade ABC efflux antibiotics are most widely used in clinic. At the same time, the AdeR/AdeS operon is strictly regulated by the upstream binary control system (AdeR/AdeS). The gene Ade R/Ade S of the binary regulatory system showed base mutation and resulted in amino acid mutation, which resulted in a significant up-regulation of ade B expression in the efflux pump gene. This may ultimately lead to a general increase in the rate of drug resistance of Acinetobacter baumannii.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R446.5
本文编号：2196493
[Abstract]:Acinetobacter baumannii (Acinetobacter baumannii) (Acinetobacter baumannii) is a common opportunistic pathogen in hospitals, which is closely related to the infection of severe patients. It often causes ventilator-associated pneumonia, urinary tract infection, septicemia, wound infection and central nervous system infection. Acinetobacter baumannii has low nutritional requirements and can easily survive and spread on the surface of objects in the hospital environment, resulting in an outbreak of nosocomial infection. Pubmed's latest data show that the clone complex 92 (Clonal complex 92 CC92 is found in Asia, Europe, and America. Australia and other countries, as well as most parts of China, are the most prevalent clone complexes in the world. In addition, the drug resistance of Acinetobacter baumannii can not be ignored. The widespread use of antibiotics and the easy spread of drug resistance genes among different Acinetobacter baumannii make the drug resistance rate increase. The factors such as large area skin defect, interventional operation, extensive use of broad-spectrum antibiotics and low immunity of severe burn patients all provide a good opportunity for the invasion of Acinetobacter baumannii. During the period 2011-2012, we studied the isolation and drug resistance of strains from the clinical microorganism samples of severe patients in the Department of Burns, first affiliated Hospital of the third military Medical University. The results showed that the isolation rate of Acinetobacter baumannii was 34. 4% and the resistance rate to carbapenem antibiotics was 89. 5% in severe patients. We then screened Acinetobacter baumannii in the intensive care unit environment and isolated Acinetobacter baumannii from the patient's bed unit, ECG monitor buttons, infusion pump buttons, and the hands of health care workers. However, is there a correlation between Acinetobacter baumannii in patients' clinical microbial samples and Acinetobacter baumannii in ward settings? Why is the drug resistance rate so high? These problems are an unknown. This study focuses on these two problems. In this study, the genotyping of Acinetobacter baumannii isolated from clinical microorganism samples and environmental samples of patients with severe burn was carried out by Pulsed-field gel electrophoresis-PFGE and Multi-locus sequence typing. The results showed that the four main types of PFGE were Glutathione Igna H and MLST were mainly ST368 / ST369 / ST195 and ST191. The main types of the two different typing methods were patient and ward environment samples. In addition to genotyping, we also studied the mechanism of 尾-lactam antibiotic resistance in these two strains from different sources. These include the most common 尾 -lactamase resistance genes of Acinetobacter baumannii and the most complex efflux pump mechanisms. The detection rates of blaAmp C and blaOXA-23 of bla Perot B and D were higher in both patient samples and ward samples. The detection rate of blaOXA-51 in D group was 100%. In Acinetobacter baumannii efflux pump, Ade ABC efflux antibiotics are most widely used in clinic. At the same time, the AdeR/AdeS operon is strictly regulated by the upstream binary control system (AdeR/AdeS). The gene Ade R/Ade S of the binary regulatory system showed base mutation and resulted in amino acid mutation, which resulted in a significant up-regulation of ade B expression in the efflux pump gene. This may ultimately lead to a general increase in the rate of drug resistance of Acinetobacter baumannii.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R446.5
【参考文献】
相关期刊论文 前1条
1 李孝权;李钏华;胡玉山;邓志爱;庞杏林;张欣强;张健;张颖;肖扬;莫自耀;陈守义;王鸣;;广州地区食品分离空肠弯曲菌的病原及分子分型分析[J];热带医学杂志;2008年08期
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