苏州地区呼吸道感染儿童肺炎链球菌携带率、耐药现状和分子流行病学研究

发布时间：2018-03-21 16:40

  本文选题：肺炎链球菌　切入点：携带率　出处：《复旦大学》2014年硕士论文　论文类型：学位论文

【摘要】：背景：肺炎链球菌(Streptococcus pneumoniae, S.peumoniae, SP)是人体鼻咽部的正常菌群,是引起呼吸道感染的主要致病菌,也是导致5岁以下儿童生病住院和死亡的重要原因,给家庭和社会均造成了极大的负担。近年来,在抗生素的选择压力下,肺炎链球菌对青霉素和大环内酯类抗生素的耐药率呈现迅速增长的趋势。此外,多重耐药菌株的出现和流行使全球控制SP感染的形势更为严峻。而国际流行耐药(Pneumococcal Molecular Epidemiology Network, PMEN)克隆株的传播是肺炎链球菌耐药率增加和多重耐药菌株流行的主要原因。第一部分呼吸道感染儿童肺炎链球菌的携带率研究目的：了解苏州地区5岁以下呼吸道感染住院患儿鼻咽部的肺炎链球菌携带情况,并分析肺炎链球菌携带的影响因素,为确定肺炎链球菌感染的高危人群和制定相关防控策略提供科学依据。方法：收集2012-2013年苏州大学附属儿童医院5岁以下呼吸道感染住院患儿的痰液标本,并对其进行细菌学检测。通过医院HIS系统查询病人的年龄、入院日期、性别和疾病诊断等信息。采用Logistic回归模型分析肺炎链球菌携带的影响因素。结果：2012-2013年,5岁以下呼吸道感染住院患儿共有16570例,其中63.1%的病例为男童。病例主要集中在2岁以下的幼龄儿童。住院病例数随患儿年龄的增长而减少。肺炎是所有呼吸道感染病例中最常见的疾病。冬春两季的呼吸道感染病人数最多。肺炎链球菌的携带率为12.4%。多因素Logistic回归分析显示：2013年的SP带菌率高于2012年(OR=1.20,95%CI:1.09-1.32);女童患儿的SP带菌率低于男童(OR=0.86,95%CI:0.78-0.95);带菌率随年龄增长而增加(OR=1.38,95%CI：1.33-1.42)；下呼吸道感染患儿的带菌率高于上呼吸道感染患儿(OR=1.55,95%CI：1.09-2.22)。结论：住院患儿的肺炎链球菌携带受入院年份、患儿性别、年龄和疾病种类等因素的影响。由于患儿肺炎链球菌携带率随年龄增长而增加,因此应重点关注学龄前儿童的携带情况,并针对该人群制定有效的预防策略。第二部分 呼吸道感染儿童肺炎链球菌的耐药性研究目的：了解2012-2013年苏州地区呼吸道感染住院患儿肺炎链球菌分离株的耐药谱和耐药模式,分析苏州地区儿童肺炎链球菌的耐药现状,以期指导临床合理用药。方法：采用Kirby-Bauer纸片扩散试验和E-test法对收集到的2053株肺炎链球菌分离株进行敏感性试验。结果：肺炎链球菌对红霉素和克林霉素不敏感率分别高达99.7%和98.2%；对青霉素、阿莫西林、头孢噻肟和头孢曲松等4种β内酰胺类抗生素的不敏感分别为32.7%、36.6%、48.5%和51.1%；对左氧氟沙星、莫西沙星等非常规抗生素的不敏感率很低。肺炎链球菌对β内酰胺类抗生素存在交叉耐药。与2岁患儿相比,2-5岁患儿肺炎链球菌对β内酰胺类抗生素的不敏感率更高(OR：1.267,95%CI：1.051-1.526)。肺炎链球菌的多重耐药率高达98.3%,耐药模式主要为红霉素+β内酰胺类抗生素+复方新诺明+克林霉素+四环素。结论：苏州地区儿童肺炎链球菌的耐药情况非常严重,且呈多重耐药模式。本研究结果对临床治疗肺炎链球菌疾病和抗生素的选择具有参考价值,且提示临床需合理使用抗生素。第二部分 呼吸道感染儿童肺炎链球菌的耐药性研究目的：了解2012-2013年苏州地区呼吸道感染住院患儿肺炎链球菌分离株的耐药谱和耐药模式,分析苏州地区儿童肺炎链球菌的耐药现状,以期指导临床合理用药。方法：采用Kirby-Bauer纸片扩散试验和E-test法对收集到的2053株肺炎链球菌分离株进行敏感性试验。结果：肺炎链球菌对红霉素和克林霉素不敏感率分别高达99.7%和98.2%；对青霉素、阿莫西林、头孢噻肟和头孢曲松等4种β内酰胺类抗生素的不敏感分别为32.7%、36.6%、48.5%和51.1%；对左氧氟沙星、莫西沙星等非常规抗生素的不敏感率很低。肺炎链球菌对β内酰胺类抗生素存在交叉耐药。与2岁患儿相比,2-5岁患儿肺炎链球菌对β内酰胺类抗生素的不敏感率更高(OR：1.267,95%CI：1.051-1.526)。肺炎链球菌的多重耐药率高达98.3%,耐药模式主要为红霉素+β内酰胺类抗生素+复方新诺明+克林霉素+四环素。结论：苏州地区儿童肺炎链球菌的耐药情况非常严重,且呈多重耐药模式。本研究结果对临床治疗肺炎链球菌疾病和抗生素的选择具有参考价值,且提示临床需合理使用抗生素。第三部分 呼吸道感染儿童肺炎链球菌的分子流行病学研究目的：了解肺炎链球菌分离株的分子特征,如血清型分布、大环内酯类药物的耐药机制和序列分型等,分析国际流行耐药(PMEN)克隆株的流行情况,追踪PMEN克隆株的起源和进化路径。方法：对2012年7月-2013年12月期间苏州大学附属儿童医院住院治疗的呼吸道感染患儿分离的290株肺炎链球菌菌株,采用多重PCR方法鉴定菌株血清型,利用PCR方法检测大环内酯类抗生素耐药基因ermB和mefA/E,利用多位点序列分型(Multilocus Sequence Typing, MLST)进行基因分型。结果：本研究检测出3株同时携带19A和6B两种血清型的共同定植株。19F、6B、23F和19A是4种最主要的血清型。PCV7和PCV13血清型的覆盖率分别为72.8%和87.8%。菌株基因分型共检测出75种序列分型(Sequence Types, STs),其中ST271、ST320和ST81是最主要的3种STs。经与PMEN比对,研究共发现10种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%)最为流行。PMEN克隆株对β内酰胺类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克隆株同时携带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克隆株对β内酰胺类抗生素的不敏感率最高(青霉素：66.9%,头孢噻肟：79.0%,阿莫西林：79.8%),其共同携带ermB和mefA/E基因的比例最高(98.4%)。结论：苏州地区PMEN克隆株流行以PMEN14克隆株为主,多种PMEN克隆株共存。PMEN14克隆株的播散是引起苏州地区β内酰胺类抗生素耐药主要原因。考虑到]PMEN14克隆株主要与19群血清型相关,建议在儿童人群中引入PCV13的免疫接种,以阻断PMEN14克隆株的传播。
[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. 绌剁洰鐨勶細浜嗚В2012-2013骞磋嫃宸炲湴鍖哄懠鍚搁亾鎰熸煋浣忛櫌鎮ｅ効鑲虹値閾剧悆鑿屽垎绂绘牚鐨勮，

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