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全国县级医院门诊分离大肠埃希菌超广谱β-内酰胺酶分子型别与流行病学研究

发布时间:2019-05-30 02:34
【摘要】:研究背景及目的 在中国已经有多项研究阐明在三级医院中产超广谱p-内酰胺酶(extended-spectrum beta-lactamases, ESBLs)肠杆菌科细菌的流行特征,产ESBL的大肠埃希菌呈不断上升趋势,2000-2011年期间阳性率从不到20%上升到60%以上。然而这些研究都是针对城市中的三级医院,没有针对中国基层和地方医院的社区相关的感染的相关研究。本课题主要目的是研究中国县级医院门诊分离的大肠埃希菌中ESBLs和AmpC酶的流行状况、分子特征和地区分布的特点。 研究方法 收集30家县级医院2010年8月到2011年8月一年期间门诊感染患者大肠埃希菌。所有药敏实验均根据CLSI推荐的琼脂稀释法进行。采用PCR的方法检测ESBLs和AmpC基因,并通过测序进行确认。所有ESBLs阳性的菌株都应用MLST的方法进行克隆分型。 研究结果 共收集了550株大肠埃希菌,对比阿培南、亚胺培南、美罗培南均敏感,94.1%和93.6%的菌株对磷霉素和阿米卡星敏感,91%的菌株对哌拉西林/他唑巴坦敏感,而只有47.6%和50.6%的菌株对头孢唑林和头孢呋辛敏感,80.4%的菌株对头孢他啶敏感,对环丙沙星和左氧氟沙星的敏感率分别为46%和48.4%。550株大肠埃希菌中经ESBL表型确认试验有249株(45.3%)为表型阳性。表型阳性的菌株中都对氨苄西林耐药,99.6%(248株)对头孢唑林耐药,对头孢呋辛、头孢曲松、和氨苄西林/舒巴坦的耐药率分别为98.8%,98.8%和61.5%,分别有73.3%和68.9%的菌株对环丙沙星和左氧氟沙星耐药,对哌拉西林的耐药率为91%,但对哌拉西林/他唑巴坦的耐药率仅有4.5%,对磷霉素和阿米卡星的敏感性较高,敏感率分别为88.6%和89.1%。 256株(46.5%)菌株携带ESBLs基因,不同地区ESBLs基因阳性率从30.2%到57.0%。共检测到12种blaCTX-M基因的亚型,其中最常见的基因型为:baCTX-M-14(163/256,64.5%), blaCTX-M-55(47/256,18.4%)和blaCTX-M-15(31/256,12.1%),其中发现CTX-M-55型的耐药基因阳性率超过CTX-M-15在我国属首次。检出率较高的广谱β-内酰胺酶基因分别是blaTEM-1(347株),blaOXA-1(35株)和blaSHV-11(5株),作为单一基因或与其他超广谱酶基因共存。一株携带blaCTX-M-55基因,但是表型试验显示阴性,基因检测发现该菌株同时β-内酰胺酶抑制剂耐药TEM基因,TEM-30。共有11株大肠埃希菌携带CMY-2类的AmpC酶,其中三株同时携带blaCTX-M.256株产ESBL的菌株中共检测到了64个ST型别,其中包括9个新的ST型。ST131为最流行的型别,占10.5%,其他常见的分别是ST69(14/256,5.5%),ST405(14/256,5.5%)和ST38(12/256,4.7%)。 结论 1.我国县级医院门诊患者分离的大肠埃希菌普遍存在多重耐药菌,尤其是对β-内酰胺和喹诺酮类药物的耐药,ESBLs阳性的菌株中对环丙沙星和左氧氟沙星的耐药率已经达到73.3%和68.9%。 2.我国社区感染患者中产ESBL大肠埃希菌较高的检出率,基层医院社区感染与三级医院细菌ESBL是酶型相似,总体都是以产CTX-M-14型为主,但是本研究中发现多家医院产酶型别以CTX-M-55型为主。 3.首次发现在中国CTX-M-55型的广泛流行,并取代之前较流行的CTX-M-15型成为第二流行的型别。 4.在中国县级医院门诊病人中最常见的大肠埃希菌是ST131,占10.9%,总体ST型别呈不规律分散分布,没有进化集中趋势。在西北地区出现了ST38的集中流行趋势,需要进一步的研究来明确其传播机制。 5.首次在中国的肠杆菌科细菌中发现OXA-10也需要引起重视,明确何种机制导致本来在铜绿假单胞菌中检出的耐药基因目前播散到肠杆菌科细菌中。 6.全国7个地区产ESBLs阳性率有明显差异,其中最高的是华北地区57%,最低的为华东地区仅有30.2%;虽然产酶型别总体上是以CTX-M-14型,一些医院以CTX-M-1组的CTX-M-55型和CTX-M-15型为主要流行型别,这说明在我国各地区产酶的情况复杂,未来更需要重视探索不同地区甚至不同医院对产ESBLs菌株感染患者经验治疗的最佳方案。
[Abstract]:Background and purpose of the study In China, a number of studies have been conducted to illustrate the prevalence of the bacteria of the enterobacteriaceae in the three-level hospital, and the E. coli producing ESBL is increasing. The positive rate for the period 2000-2011 increased from less than 20 per cent to 60 per cent. However, these studies are directed to three-level hospitals in the city, and there is no relevant research on community-related infections in the Chinese and local hospitals The main purpose of this study is to study the prevalence, molecular and regional distribution of ESBLs and AmpC enzymes in E. coli isolated from the outpatients in the Chinese county hospital. Point. The study method collected 30 county-level hospitals from August 2010 to August 2011 for outpatient infection E. coli. All drug sensitivity experiments were based on the CLSI-recommended agar The dilution method was performed. The ESBLs and AmpC genes were detected by the PCR method and tested by the test The sequence was confirmed. All ESBLs-positive strains applied the MLST method. line clone The results showed that 550 strains of E. coli were collected, and the strains were sensitive to meropenem, imipenem and meropenem. The strains of 94.1% and 93.6% were sensitive to fosfomycin and amikacin.91% of the strains were sensitive to the strains. Only 47.6% and 50.6% of the strains were sensitive to ceftriaxine and cefosinine, and 80.4% of the strains were sensitive to ceftriaxil, and the sensitivity to ciprofloxacin and levofloxacin was 46% and 48.4%, respectively.249 strains (45%) were identified in 550 strains of E. coli with ESBL phenotype. (3%) of the strains were positive for phenotypic positive. The resistance rate of ceftazlocillin, ceftriaxone, and methicillin/ sulbactam was 98.8%, 98.8% and 61.5%, respectively, and 73.3% and 68.9% of the strains of ceftriaxine, ceftriaxone, and methicillin/ sulbactam were 98.8%, 98.8% and 61.5%, respectively. The resistance rate of both the star and levofloxacin is 91%, but the resistance rate of the methicillin/ tazlocillin is only 4.5%, the sensitivity to the fosfomycin and the amikacin is high, the sensitivity rate is 88, 6% and 89.1%.256 (46.5%) strains carried the ESBLs gene, and the positive rate of ESBLs in different regions was higher than that of ESBLs. 30.2% to 57.0%. A total of 12 subtypes of the blaCTX-M gene were detected, among which the most common genotypes were: baCTX-M-14 (163/256, 64.5%), blaCTX-M-55 (47/256, 18.4%) and blaCTX-M-15 (31/256, 12.1%), in which the positive rate of the drug-resistant gene of type CTX-M-55 was found to exceed CTX -M-15 was the first in our country. The high detection rate of the broad-spectrum I-aminidase gene was blaTEM-1 (347 strains), blaOXA-1 (35 strains) and blaSHV-11 (5 strains) as a single gene or Coexistence with other super-broad-spectrum enzyme genes. A blaCTX-M-55 gene is carried, but the phenotypic test is negative, and the gene detection shows that the strain is also resistant to the resistance of the inhibitor of the aminidase inhibitor at the same time. The EM gene, TEM-30, and 11 strains of E. coli carrying the AmpC-2-type AmpC enzyme, three of which simultaneously carried the blaCTX-M.256 strains of ESBL-producing strain,64 ST-type strains were detected. These include 9 new ST-types. ST131 is the most popular type, accounting for 10.5%, and other common ST69 (14/256, 5.5%), ST405 (14/256, 5.5%), and ST38 (1 2/ Conclusion 1. The drug-resistant rate of ciprofloxacin and levofloxacin in E. coli isolated from outpatients in the county-level hospital in China, especially the drug-resistant and ESBLs-positive strains of E. coli. There were 73.3% and 68.9% of ESBL.2. The positive rate of ESBL E. coli was higher in the patients with community infection in our country. The infection of the community at the grass-roots level and the bacterial ESBL of the third-class hospital were similar to that of the three-level hospital. The CTX-M-55 type is the main type of the enzyme-producing type in China.3. The first time it is found that the CTX-M-55 is popular in China, and it is more popular than before. The most common E. coli in the outpatients at the county level in China is ST131, which is 10.9%. ST-type is a non-regular distribution, and there is no evolutionary concentration trend. In the northwest, the concentration of ST38 has been found. 5. The discovery of OXA-10 in the bacteria of the Enterobacteriaceae in China for the first time is also a need for attention, and it is clear what mechanism has led to the fact that it was at the P. P. 6. The positive rate of ESBLs in 7 regions of the country was significantly different, with the highest of 57% in the North China and 30.2% in the East China. Although the enzyme-producing type was generally in the CTX-M-14 type, some hospitals were in the CTX-M-1 group. The type of TX-M-55 and CTX-M-15 is the main epidemic type, which indicates that the situation of enzyme production in various regions of China is complicated, and it is more important to focus on the exploration of different regions and even not
【学位授予单位】:浙江大学
【学位级别】:硕士
【学位授予年份】:2014
【分类号】:R515

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相关期刊论文 前1条

1 肖永红;沈萍;魏泽庆;陈云波;孔海深;杨青;张伟丽;陈晓;李兰娟;;Mohnarin 2011年度全国细菌耐药监测[J];中华医院感染学杂志;2012年22期



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