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全國縣級(jí)醫(yī)院門診分離大腸埃希菌超廣譜β-內(nèi)酰胺酶分子型別與流行病學(xué)研究

發(fā)布時(shí)間:2019-05-30 02:34
【摘要】:研究背景及目的 在中國已經(jīng)有多項(xiàng)研究闡明在三級(jí)醫(yī)院中產(chǎn)超廣譜p-內(nèi)酰胺酶(extended-spectrum beta-lactamases, ESBLs)腸桿菌科細(xì)菌的流行特征,產(chǎn)ESBL的大腸埃希菌呈不斷上升趨勢(shì),2000-2011年期間陽性率從不到20%上升到60%以上。然而這些研究都是針對(duì)城市中的三級(jí)醫(yī)院,沒有針對(duì)中國基層和地方醫(yī)院的社區(qū)相關(guān)的感染的相關(guān)研究。本課題主要目的是研究中國縣級(jí)醫(yī)院門診分離的大腸埃希菌中ESBLs和AmpC酶的流行狀況、分子特征和地區(qū)分布的特點(diǎn)。 研究方法 收集30家縣級(jí)醫(yī)院2010年8月到2011年8月一年期間門診感染患者大腸埃希菌。所有藥敏實(shí)驗(yàn)均根據(jù)CLSI推薦的瓊脂稀釋法進(jìn)行。采用PCR的方法檢測(cè)ESBLs和AmpC基因,并通過測(cè)序進(jìn)行確認(rèn)。所有ESBLs陽性的菌株都應(yīng)用MLST的方法進(jìn)行克隆分型。 研究結(jié)果 共收集了550株大腸埃希菌,對(duì)比阿培南、亞胺培南、美羅培南均敏感,94.1%和93.6%的菌株對(duì)磷霉素和阿米卡星敏感,91%的菌株對(duì)哌拉西林/他唑巴坦敏感,而只有47.6%和50.6%的菌株對(duì)頭孢唑林和頭孢呋辛敏感,80.4%的菌株對(duì)頭孢他啶敏感,對(duì)環(huán)丙沙星和左氧氟沙星的敏感率分別為46%和48.4%。550株大腸埃希菌中經(jīng)ESBL表型確認(rèn)試驗(yàn)有249株(45.3%)為表型陽性。表型陽性的菌株中都對(duì)氨芐西林耐藥,99.6%(248株)對(duì)頭孢唑林耐藥,對(duì)頭孢呋辛、頭孢曲松、和氨芐西林/舒巴坦的耐藥率分別為98.8%,98.8%和61.5%,分別有73.3%和68.9%的菌株對(duì)環(huán)丙沙星和左氧氟沙星耐藥,對(duì)哌拉西林的耐藥率為91%,但對(duì)哌拉西林/他唑巴坦的耐藥率僅有4.5%,對(duì)磷霉素和阿米卡星的敏感性較高,敏感率分別為88.6%和89.1%。 256株(46.5%)菌株攜帶ESBLs基因,不同地區(qū)ESBLs基因陽性率從30.2%到57.0%。共檢測(cè)到12種blaCTX-M基因的亞型,其中最常見的基因型為:baCTX-M-14(163/256,64.5%), blaCTX-M-55(47/256,18.4%)和blaCTX-M-15(31/256,12.1%),其中發(fā)現(xiàn)CTX-M-55型的耐藥基因陽性率超過CTX-M-15在我國屬首次。檢出率較高的廣譜β-內(nèi)酰胺酶基因分別是blaTEM-1(347株),blaOXA-1(35株)和blaSHV-11(5株),作為單一基因或與其他超廣譜酶基因共存。一株攜帶blaCTX-M-55基因,但是表型試驗(yàn)顯示陰性,基因檢測(cè)發(fā)現(xiàn)該菌株同時(shí)β-內(nèi)酰胺酶抑制劑耐藥TEM基因,TEM-30。共有11株大腸埃希菌攜帶CMY-2類的AmpC酶,其中三株同時(shí)攜帶blaCTX-M.256株產(chǎn)ESBL的菌株中共檢測(cè)到了64個(gè)ST型別,其中包括9個(gè)新的ST型。ST131為最流行的型別,占10.5%,其他常見的分別是ST69(14/256,5.5%),ST405(14/256,5.5%)和ST38(12/256,4.7%)。 結(jié)論 1.我國縣級(jí)醫(yī)院門診患者分離的大腸埃希菌普遍存在多重耐藥菌,尤其是對(duì)β-內(nèi)酰胺和喹諾酮類藥物的耐藥,ESBLs陽性的菌株中對(duì)環(huán)丙沙星和左氧氟沙星的耐藥率已經(jīng)達(dá)到73.3%和68.9%。 2.我國社區(qū)感染患者中產(chǎn)ESBL大腸埃希菌較高的檢出率,基層醫(yī)院社區(qū)感染與三級(jí)醫(yī)院細(xì)菌ESBL是酶型相似,總體都是以產(chǎn)CTX-M-14型為主,但是本研究中發(fā)現(xiàn)多家醫(yī)院產(chǎn)酶型別以CTX-M-55型為主。 3.首次發(fā)現(xiàn)在中國CTX-M-55型的廣泛流行,并取代之前較流行的CTX-M-15型成為第二流行的型別。 4.在中國縣級(jí)醫(yī)院門診病人中最常見的大腸埃希菌是ST131,占10.9%,總體ST型別呈不規(guī)律分散分布,沒有進(jìn)化集中趨勢(shì)。在西北地區(qū)出現(xiàn)了ST38的集中流行趨勢(shì),需要進(jìn)一步的研究來明確其傳播機(jī)制。 5.首次在中國的腸桿菌科細(xì)菌中發(fā)現(xiàn)OXA-10也需要引起重視,明確何種機(jī)制導(dǎo)致本來在銅綠假單胞菌中檢出的耐藥基因目前播散到腸桿菌科細(xì)菌中。 6.全國7個(gè)地區(qū)產(chǎn)ESBLs陽性率有明顯差異,其中最高的是華北地區(qū)57%,最低的為華東地區(qū)僅有30.2%;雖然產(chǎn)酶型別總體上是以CTX-M-14型,一些醫(yī)院以CTX-M-1組的CTX-M-55型和CTX-M-15型為主要流行型別,這說明在我國各地區(qū)產(chǎn)酶的情況復(fù)雜,未來更需要重視探索不同地區(qū)甚至不同醫(yī)院對(duì)產(chǎn)ESBLs菌株感染患者經(jīng)驗(yàn)治療的最佳方案。
[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
【學(xué)位授予單位】:浙江大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類號(hào)】:R515

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 肖永紅;沈萍;魏澤慶;陳云波;孔海深;楊青;張偉麗;陳曉;李蘭娟;;Mohnarin 2011年度全國細(xì)菌耐藥監(jiān)測(cè)[J];中華醫(yī)院感染學(xué)雜志;2012年22期



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