【作者】 马坚；

【导师】 胡必杰；

【作者基本信息】 复旦大学 ， 内科学， 2013， 硕士

【摘要】 目的比较住院前后72小时内经验性抗感染治疗是否覆盖非典型病原体,对于患者住院期间的临床疗效及经济学指标的影响。方法本研究为基于人群的、多中心、回顾性队列设计。纳入江浙沪地区4家三级医院、6家二级医院,在2010年6月1日至2011年5月31日期间符合研究设计标准的住院CAP患者。收集人口学资料、基础疾病、临床体检、实验室检查、治疗和预后等相关信息。采用统计分析比较治疗组和对照组之间临床疗效及经济学指标的差异。结果共纳入住院CAP患者827例。入院前后72小时内抗感染治疗中覆盖非典型病原体(AP覆盖组)的全因病死率为0.9%(95%CI,0.1-1.7%)显著低于对照组(抗感染治疗中覆盖非典型病原体)的4.9%(95%CI,2.6-8.2%),纠正倚偏后的相对危险度(RR)为0.18(95%CI,0.06-0.50)。主要经济学指标：AP覆盖组的住院天数(length of stay, LOS)为10.1(95%CI,9.79-10.50)天,对照组的LOS为11.6(95%CI,11.00-12.25)天,p<0.01。总的住院费用在AP覆盖组为7306.0(95%CI,6905.9-7706.2)元,显著低于对照组的9411.8(95%CI,8613.9-10209.6)元,p<0.01。直接抗菌药物费用,AP覆盖组为2653.1(95%CI,2477.6-2828.7)元,低于对照组的费用3133.0(95%CI,2860.8-3405.2)元,p<0.01。药物使用强度(DDD)在AP覆盖组为19.2(95%CI,18.3-20.2),同对照组的18.3(95%CI,17.0-19.6),p=0.28。结论抗感染治疗方案早期经验性覆盖非典型病原体有利于降低CAP患者的全因病死率，减少住院时间，降低总住院费用和抗菌药物直接费用。目的评价组合干预措施对上海市176个ICU呼吸机相关肺炎(VAP)发病率的影响。方法本研究为前-后对照研究,起止时间为2007年1月至2012年6月,分为3个阶段：基线调查、过渡期和干预期。主要VAP组合干预措施包括为加强手卫生、半卧位,采用消毒剂进行口腔护理以及对医护人员的宣教和督查。由医院感染控制专职人员收集ICU出入院人数、患者基本信息、住院天数、接受机械通气天数和VAP发病情况等资料。比较干预前、后VAP发病率,评价组合干预措施效果。结果共收集患者资料463,208例名患者资料,总计监测ICU床日数为2,535,917天,累计总机械通气日数(ventilator days, VDs)为695,185天。基线调查阶段,VAP发病率为每千VDs23.4例。实施组合干预后,VAP发病率明显开始下降,2009-2012年VAP平均发病率为每千VDs14.3例(2009-2012vs2007,RR=0.61(95%CI,0.59-0.64),RD=9.1(95%CI,8.3-9.9)。结论在ICU中施行VAP组合千预措施,可显著降低患者VAP发病率。目的通过分析嗜肺军团菌环境分离株和临床分离株在基因组水平上的差异,探索其对人类致病性的影响。方法对分离于医院环境中的嗜肺军团菌(LPE509)采用高通量Illumina技术denovo测序。。通过对测序结果进行拼接、组装后获得完整的基因组数据。采用生物信息学分析方法预测基因和可能编码的蛋白。利用OrthoMCL和Vaxign系统将LPE509基因组同已经公布序列的L.pneumophila(strains130b,570-CO-H,Alcoy, Corby, Lens, Paris, Philadelphia1)比较基因组水平的差异。结果基因组数据已经保存于GenBank,检索号为CP003885、CP003886。LPE509同其它7株已经测序的Lpneumophila存在一定相似性。LPE509基因组中发现了编码分泌系统的基因,其中包括type I secretion system(T1SS)、T2SS以及Dot/IcinT4BSS。在所有已完成测序的L.pneumophila菌株中Dot/Icm T4SSB相对保守,LPE509基因组中发现了同致病性高度相关的T4BSS的重要组分Lvh基因。7.3kbp的质粒为LPE509所特有,其中发现了可能编码多重耐药的基因。通过于其它7株序列(130b,570-CO-H, Alcoy, Corby, Lens, Paris, Philadelphia1)序列比对,LPE509编码的580,235,512,522,669,443,562为首次发现的蛋白。结论不同种属L.pneumophila基因组水平存在高度异质性,而编码分泌系统的基因,T1SS、T2SS以及Dot/Icm T4BSS目对保守。更多还原

【Abstract】 Objective Comparison of clinical efficacy and economy of empirical antibiotic regimen between covering and uncovering atypical pathogen in hospitalized patients in China.Method Population-based, multi-center, retrospective cohort study adjusting for demographics, comorbidities, and clinical characteristics.During the period from June1,2010through May31,2011, all patients presented to participated4municipal hospitals and6district hospitals were enrolled. Consistent with inclusion and exclusion criteria, data of eligible patients were collected including demographic, underling diseases, physical examination, laboratory examination, antibiotic treatment regime and prognosis. Using Logistic regression analysis to compare the main outcome and the minor outcomes between treatment group and comparator group.Results The inclusion of anti-atypical pathogen active antibiotics in initial empiric CAP treatment was associated with significantly lower mortality0.9%(95%CI,0.1-1.7%)than therapy with either a β-lactam alone (4.9%(95%CI,2.6-8.2%)), adjusted odds ratio [AOR],0.18(95%CI,0.06-0.50).Major economic index:LOS of AP covered group was10.1(95%CI,9.79-10.50), significantly less than that of comparator group10.1(95%CI,9.79-10.50). Total hospitalization expenditure in AP covered group was7306.0(95%CI,6905.9-7706.2), while which of comparator group was much higher9411.8(95%CI,8613.9-10209.6), p<0.01. Antibiotic associated expenditure was2653.1(95%CI,2477.6-2828.7) in AP covered group which was still lower than that in comparator group3133.0(95%CI,2860.8-3405.2), p<0.01. Daily defined dose in AP covered group was19.2(95%CI,18.3-20.2), is not statistically differ from that in comparator group18.3(95%CI,17.0-19.6), p=0.28. Conclusions The inclusion of anti-atypical pathogen active antibiotics in initial empiric CAP treatment was associated with improved survival, reduced IOS total hosnitalization evnenditure and antibiotic associated expenditure OBJECTIVE The aim of this study was to evaluate the effectiveness of a multidimensional infection control bundle on the reduction of incidence of ventilator-associated pneumonia (VAP) in176intensive care units (ICUs) in Shanghai.METHODS The trial was designed as a before-after study from January2007to June2012, which was divided into baseline, transition and intervention periods. VAP prevention bundle included hand hygiene, recumbent position, oral care with antiseptic, as well as education and audit the medical personnel. Number of patients, length of ICU stay, mechanical ventilator days and number of VAP cases in ICU were collected by infection control personnel. VAP rates compared in yearly periods, which used to evaluate the effectiveness of VAP control bundle. RESULTS Totally463,208patients data,2,535,917ICU bed days and695,185mechanical ventilator days(VDs) were collected in this study. Baseline VAP rate was23.4per1000ventilator days. After implementation of VAP prevention bundle, VAP rate was significantly decreased to14.3per1000ventilator days (RR0.61(95%CI,0.59-0.64), RD9.1(95%CI,8.3-9.9)).CONCLUSION Implementation of VAP prevention bundle in ICU was associated with dramatically decreasing of VAP rate in patients. OBJECIVE Analysis the difference between an environmental isolate and clinical isolates of Legionella pneumophila and explore the impacts to human pathogenesis.METHODS The genome sequence of L. pneumophila strain LPE509(LPE509) has been acquired by de novo sequencing by Illumina. The complete genomic data has been achieved after assembling the contigs. Bioinformatic methods were applied to predict putative genes and proteins. Genome comparison between LPE509and the other known L. pneumophila genomes (strains130b,570-CO-H, Alcoy, Corby, Lens, Paris, Philadelphia1) was performed with OrthoMCL and Vaxign that incorporates Ortho MCL.RESULTS The genome sequence of LPE509has been deposited at GenBank under accession number CP003885and CP003886. Gene organization of LPE509is highly syntenic with those of the seven sequenced L. pneumophila strains. Gene clusters encoding all the structural components of the type I secretion system (T1SS), the T2SS, and the Dot/Icm T4BSS were found in syntenic positions. Of the277experimentally verified protein substrates the Dot/Icm transporter (7,13),274are present in the LPE509genome. In addition to the7.3kbp plasmid unique to strain LPE509which codes for genes putatively involved in resistance to multiple drugs. We found that comparing to the other7sequenced strains (130b,570-CO-H, Alcoy, Corby, Lens, Paris, Philadelphia1), strain LPE509codes for580,235,512,522,669,443,562unique proteins. CONCLUSION Highlighting the high levels of genomic plasticity among different L. pneumophila isolates, T1SS, T2SS, and the Dot/Icm T4BSS found to be relatively conservative.更多还原