重癥燒傷病房鮑曼不動桿菌的分子流行病學研究
發(fā)布時間：2018-08-22 08:01
【摘要】：鮑曼不動桿菌(Acinetobacter baumannii)是醫(yī)院常見的條件致病菌,與重癥患者的感染密切相關,常引起呼吸機相關性肺炎、尿路感染、敗血癥、創(chuàng)口感染及中樞神經系統(tǒng)感染等。鮑曼不動桿菌營養(yǎng)要求低,極易在醫(yī)院環(huán)境的物體表面存活和傳播,從而導致醫(yī)院感染的暴發(fā)流行。Pubmed最新的數據顯示,克隆復合體92(Clonal complex 92,CC92)遍布了亞洲、歐洲、美洲、澳洲等多個國家以及中國的大部分地區(qū),是全球流行最為廣泛的克隆復合體。除此之外,鮑曼不動桿菌的耐藥問題也不容忽視,抗生素的廣泛運用及耐藥基因容易在不同鮑曼不動桿菌之間水平傳播使得耐藥率不斷增加。重癥燒傷患者大面積皮膚缺損、介入性操作、廣譜抗生素的廣泛運用以及重癥燒傷患者免疫力低下等因素都為鮑曼不動桿菌的入侵提供了良好的機會。在2011-2012年期間,我們對第三軍醫(yī)大學第一附屬醫(yī)院燒傷科重癥患者臨床微生物樣本的菌株分離和耐藥情況進行了研究,結果顯示重癥患者鮑曼不動桿菌分離率高達34.4%,對碳青霉烯類抗生素耐藥率高達89.5%。隨后,我們對重癥病房環(huán)境中的鮑曼不動桿菌進行了篩查,在患者的床單元、心電監(jiān)護儀按鈕、輸液泵按鈕以及醫(yī)護人員的手上均分離出了鮑曼不動桿菌。然而,患者臨床微生物樣本中的鮑曼不動桿菌和病房環(huán)境中的鮑曼不動桿菌之間是否有相關性?為何耐藥率如此之高?這些問題都是一個未知數。本研究主要圍繞這兩個問題展開。本研究通過脈沖場電泳(Pulsed-field gel electrophoresis,PFGE)和多位點序列分析(Multi-locus sequence typing,MLST)兩種技術對重癥燒傷患者臨床微生物樣本及病房環(huán)境樣本中分離的鮑曼不動桿菌進行基因分型。結果顯示,PFGE以G、F、I、H這四個型別為主,MLST以ST368、ST369、ST195和ST191為主,兩種不同分型方法的主要型別中均有患者和病房環(huán)境樣本的檢出。除了基因分型以外,我們還對這兩種不同來源菌株的β-內酰胺類抗生素耐藥機制進行了初探,其中包括鮑曼不動桿菌最常見的β-內酰胺酶耐藥基因和最為復雜的外排泵機制。β-內酰胺酶耐藥基因檢測結果顯示,無論是患者樣本還是病房樣本,A類的bla PER、B類的blaVIM、C類的blaAmp C和D類的blaOXA-23均有較高的檢出率,其中D類的blaOXA-51檢出率100%。鮑曼不動桿菌的外排泵中,Ade ABC外排的抗生素在臨床上運用最為廣泛。同時,adeABC操縱子還受上游二元調控系統(tǒng)AdeR/AdeS的嚴格調控。該二元調控系統(tǒng)編碼基因Ade R/Ade S均出現了堿基的突變且導致了氨基酸的突變,并引起了外排泵基因ade B表達量明顯上調,這可能是最終導致鮑曼不動桿菌耐藥率普遍升高的原因。
[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.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R446.5
本文編號：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.
【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R446.5
【參考文獻】
相關期刊論文 前1條
1 李孝權;李釧華;胡玉山;鄧志愛;龐杏林;張欣強;張健;張穎;肖揚;莫自耀;陳守義;王鳴;;廣州地區(qū)食品分離空腸彎曲菌的病原及分子分型分析[J];熱帶醫(yī)學雜志;2008年08期
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