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蘇州地區(qū)呼吸道感染兒童肺炎鏈球菌攜帶率、耐藥現(xiàn)狀和分子流行病學(xué)研究

發(fā)布時(shí)間:2018-03-21 16:40

  本文選題:肺炎鏈球菌 切入點(diǎn):攜帶率 出處:《復(fù)旦大學(xué)》2014年碩士論文 論文類型:學(xué)位論文


【摘要】:背景:肺炎鏈球菌(Streptococcus pneumoniae, S.peumoniae, SP)是人體鼻咽部的正常菌群,是引起呼吸道感染的主要致病菌,也是導(dǎo)致5歲以下兒童生病住院和死亡的重要原因,給家庭和社會(huì)均造成了極大的負(fù)擔(dān)。近年來,在抗生素的選擇壓力下,肺炎鏈球菌對(duì)青霉素和大環(huán)內(nèi)酯類抗生素的耐藥率呈現(xiàn)迅速增長(zhǎng)的趨勢(shì)。此外,多重耐藥菌株的出現(xiàn)和流行使全球控制SP感染的形勢(shì)更為嚴(yán)峻。而國(guó)際流行耐藥(Pneumococcal Molecular Epidemiology Network, PMEN)克隆株的傳播是肺炎鏈球菌耐藥率增加和多重耐藥菌株流行的主要原因。第一部分呼吸道感染兒童肺炎鏈球菌的攜帶率研究目的:了解蘇州地區(qū)5歲以下呼吸道感染住院患兒鼻咽部的肺炎鏈球菌攜帶情況,并分析肺炎鏈球菌攜帶的影響因素,為確定肺炎鏈球菌感染的高危人群和制定相關(guān)防控策略提供科學(xué)依據(jù)。方法:收集2012-2013年蘇州大學(xué)附屬兒童醫(yī)院5歲以下呼吸道感染住院患兒的痰液標(biāo)本,并對(duì)其進(jìn)行細(xì)菌學(xué)檢測(cè)。通過醫(yī)院HIS系統(tǒng)查詢病人的年齡、入院日期、性別和疾病診斷等信息。采用Logistic回歸模型分析肺炎鏈球菌攜帶的影響因素。結(jié)果:2012-2013年,5歲以下呼吸道感染住院患兒共有16570例,其中63.1%的病例為男童。病例主要集中在2歲以下的幼齡兒童。住院病例數(shù)隨患兒年齡的增長(zhǎng)而減少。肺炎是所有呼吸道感染病例中最常見的疾病。冬春兩季的呼吸道感染病人數(shù)最多。肺炎鏈球菌的攜帶率為12.4%。多因素Logistic回歸分析顯示:2013年的SP帶菌率高于2012年(OR=1.20,95%CI:1.09-1.32);女童患兒的SP帶菌率低于男童(OR=0.86,95%CI:0.78-0.95);帶菌率隨年齡增長(zhǎng)而增加(OR=1.38,95%CI:1.33-1.42);下呼吸道感染患兒的帶菌率高于上呼吸道感染患兒(OR=1.55,95%CI:1.09-2.22)。結(jié)論:住院患兒的肺炎鏈球菌攜帶受入院年份、患兒性別、年齡和疾病種類等因素的影響。由于患兒肺炎鏈球菌攜帶率隨年齡增長(zhǎng)而增加,因此應(yīng)重點(diǎn)關(guān)注學(xué)齡前兒童的攜帶情況,并針對(duì)該人群制定有效的預(yù)防策略。第二部分 呼吸道感染兒童肺炎鏈球菌的耐藥性研究目的:了解2012-2013年蘇州地區(qū)呼吸道感染住院患兒肺炎鏈球菌分離株的耐藥譜和耐藥模式,分析蘇州地區(qū)兒童肺炎鏈球菌的耐藥現(xiàn)狀,以期指導(dǎo)臨床合理用藥。方法:采用Kirby-Bauer紙片擴(kuò)散試驗(yàn)和E-test法對(duì)收集到的2053株肺炎鏈球菌分離株進(jìn)行敏感性試驗(yàn)。結(jié)果:肺炎鏈球菌對(duì)紅霉素和克林霉素不敏感率分別高達(dá)99.7%和98.2%;對(duì)青霉素、阿莫西林、頭孢噻肟和頭孢曲松等4種β內(nèi)酰胺類抗生素的不敏感分別為32.7%、36.6%、48.5%和51.1%;對(duì)左氧氟沙星、莫西沙星等非常規(guī)抗生素的不敏感率很低。肺炎鏈球菌對(duì)β內(nèi)酰胺類抗生素存在交叉耐藥。與2歲患兒相比,2-5歲患兒肺炎鏈球菌對(duì)β內(nèi)酰胺類抗生素的不敏感率更高(OR:1.267,95%CI:1.051-1.526)。肺炎鏈球菌的多重耐藥率高達(dá)98.3%,耐藥模式主要為紅霉素+β內(nèi)酰胺類抗生素+復(fù)方新諾明+克林霉素+四環(huán)素。結(jié)論:蘇州地區(qū)兒童肺炎鏈球菌的耐藥情況非常嚴(yán)重,且呈多重耐藥模式。本研究結(jié)果對(duì)臨床治療肺炎鏈球菌疾病和抗生素的選擇具有參考價(jià)值,且提示臨床需合理使用抗生素。第二部分 呼吸道感染兒童肺炎鏈球菌的耐藥性研究目的:了解2012-2013年蘇州地區(qū)呼吸道感染住院患兒肺炎鏈球菌分離株的耐藥譜和耐藥模式,分析蘇州地區(qū)兒童肺炎鏈球菌的耐藥現(xiàn)狀,以期指導(dǎo)臨床合理用藥。方法:采用Kirby-Bauer紙片擴(kuò)散試驗(yàn)和E-test法對(duì)收集到的2053株肺炎鏈球菌分離株進(jìn)行敏感性試驗(yàn)。結(jié)果:肺炎鏈球菌對(duì)紅霉素和克林霉素不敏感率分別高達(dá)99.7%和98.2%;對(duì)青霉素、阿莫西林、頭孢噻肟和頭孢曲松等4種β內(nèi)酰胺類抗生素的不敏感分別為32.7%、36.6%、48.5%和51.1%;對(duì)左氧氟沙星、莫西沙星等非常規(guī)抗生素的不敏感率很低。肺炎鏈球菌對(duì)β內(nèi)酰胺類抗生素存在交叉耐藥。與2歲患兒相比,2-5歲患兒肺炎鏈球菌對(duì)β內(nèi)酰胺類抗生素的不敏感率更高(OR:1.267,95%CI:1.051-1.526)。肺炎鏈球菌的多重耐藥率高達(dá)98.3%,耐藥模式主要為紅霉素+β內(nèi)酰胺類抗生素+復(fù)方新諾明+克林霉素+四環(huán)素。結(jié)論:蘇州地區(qū)兒童肺炎鏈球菌的耐藥情況非常嚴(yán)重,且呈多重耐藥模式。本研究結(jié)果對(duì)臨床治療肺炎鏈球菌疾病和抗生素的選擇具有參考價(jià)值,且提示臨床需合理使用抗生素。第三部分 呼吸道感染兒童肺炎鏈球菌的分子流行病學(xué)研究目的:了解肺炎鏈球菌分離株的分子特征,如血清型分布、大環(huán)內(nèi)酯類藥物的耐藥機(jī)制和序列分型等,分析國(guó)際流行耐藥(PMEN)克隆株的流行情況,追蹤PMEN克隆株的起源和進(jìn)化路徑。方法:對(duì)2012年7月-2013年12月期間蘇州大學(xué)附屬兒童醫(yī)院住院治療的呼吸道感染患兒分離的290株肺炎鏈球菌菌株,采用多重PCR方法鑒定菌株血清型,利用PCR方法檢測(cè)大環(huán)內(nèi)酯類抗生素耐藥基因ermB和mefA/E,利用多位點(diǎn)序列分型(Multilocus Sequence Typing, MLST)進(jìn)行基因分型。結(jié)果:本研究檢測(cè)出3株同時(shí)攜帶19A和6B兩種血清型的共同定植株。19F、6B、23F和19A是4種最主要的血清型。PCV7和PCV13血清型的覆蓋率分別為72.8%和87.8%。菌株基因分型共檢測(cè)出75種序列分型(Sequence Types, STs),其中ST271、ST320和ST81是最主要的3種STs。經(jīng)與PMEN比對(duì),研究共發(fā)現(xiàn)10種PMEN克隆株,其中PMEN14克隆株(42.8%)、PMEN1克隆株(10.7%)和PMEN37克隆株(6.6%)最為流行。PMEN克隆株對(duì)β內(nèi)酰胺類抗生素的不敏感率高于非PMEN克隆株(x2PEN=29.239,PPEN0.001; x2CTX=29.682, PCTX0.001; x2AMX=36.442,PAMX0.001),且PMEN克隆株同時(shí)攜帶ermB和mefA/E基因的比例也高于非PMEN克隆株(70.6% vs.34.9%, x2=36.084, P0.001)。在所有PMEN克隆株中,PMEN14克隆株對(duì)β內(nèi)酰胺類抗生素的不敏感率最高(青霉素:66.9%,頭孢噻肟:79.0%,阿莫西林:79.8%),其共同攜帶ermB和mefA/E基因的比例最高(98.4%)。結(jié)論:蘇州地區(qū)PMEN克隆株流行以PMEN14克隆株為主,多種PMEN克隆株共存。PMEN14克隆株的播散是引起蘇州地區(qū)β內(nèi)酰胺類抗生素耐藥主要原因?紤]到]PMEN14克隆株主要與19群血清型相關(guān),建議在兒童人群中引入PCV13的免疫接種,以阻斷PMEN14克隆株的傳播。
[Abstract]:Background: Streptococcus pneumoniae (Streptococcus, pneumoniae, S.peumoniae, SP) is the normal flora of the nasopharynx, the main pathogens causing respiratory tract infection in children under 5 years old, is the leading cause of illness and death in an important reason, to the family and society have caused great burden. In recent years, under the selective pressure of antibiotics and the resistance of Streptococcus pneumoniae to penicillin and macrolide antibiotic rate showed the trend of rapid growth. In addition, emergence and prevalence of drug-resistant strains of the global control of SP infection situation is more severe. And the international popular resistance (Pneumococcal Molecular Epidemiology Network, PMEN) is the main reason for the spread of clones of Streptococcus pneumoniae resistance rate increase and multi drug resistant strains. The purpose of the study is to pop the carrying rate of pediatric pneumococcal respiratory tract infection: the first part about Suzhou area under the age of 5 Carrying status of hospitalized children with respiratory tract infection of nasopharyngeal Streptococcus pneumoniae, Streptococcus pneumoniae, and analyze the influence factors of carrying, in order to identify high risk population of Streptococcus pneumoniae infection and provide scientific basis for the formulation of relevant prevention and control strategy. Methods: the sputum samples were collected from 2012-2013 hospitalized children with respiratory tract infection in Children's Hospital Affiliated to Suzhou University under the age of 5, and the bacteriological detection. Through query the age of the patient, the hospital HIS system date of admission, gender and disease diagnosis information. Using Logistic regression model to analyze the influencing factors of Streptococcus pneumoniae carried. Results: 2012-2013 years, a total of 16570 cases of hospitalized children with respiratory tract infection at the age of 5, of which 63.1% cases were boys. The cases were mainly concentrated in children younger than 2 years. The number of inpatients with children age decreased. Pneumonia is the most common in all cases of respiratory tract infection The largest number of disease disease. In the two season of respiratory tract infection. Streptococcus pneumoniae carrying rate of Logistic 12.4%. regression analysis showed that: in 2013 the SP carrier rate is higher than in 2012 (OR=1.20,95%CI:1.09-1.32); the SP carrier rate is lower than that of girls with boys (OR=0.86,95%CI: 0.78-0.95); the infection rate increased with age (OR=1.38,95%CI:1.33-1.42); infected children lower respiratory tract infection rate is higher than that of children with upper respiratory tract infection (OR=1.55,95%CI:1.09-2.22). Conclusion: the hospitalized children with Streptococcus pneumoniae carried by children with gender, admission time, age and disease types and other factors. Due to Streptococcus pneumoniae in children with positive rate increased with age, so it should focus on the carrying situation of preschool children, and for the the population to develop effective prevention strategies. Drug resistance of Streptococcus pneumoniae in children second respiratory tract infection. 絀剁洰鐨勶細(xì)浜?jiǎn)瑙?012-2013騫磋嫃宸炲湴鍖哄懠鍚擱亾鎰熸煋浣忛櫌鎮(zhèn)e効鑲虹値閾劇悆鑿屽垎紱繪牚鐨勮,

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