住院患者艰难梭菌无症状感染的危险因素分析

目的 分析住院患者无症状感染艰难梭菌的毒力特征及危险因素,为艰难梭菌感染(CDI)性腹泻的防治提供理论依据。方法 收集住院患者的粪便标本。将其中的CDI患者分为CDI有腹泻组和CDI无腹泻组,将无腹泻症状且艰难梭菌培养阴性患者设为对照组。收集患者临床资料,将粪便标本进行艰难梭菌分离培养并进行艰难梭菌毒素检测,对临床资料及检测结果进行统计学分析。结果 CDI有腹泻组毒素蛋白阳性率高于CDI无腹泻组(P<0.05)。多因素Logistic回归分析显示：使用抑酸剂、2个月内使用头孢菌素类抗菌药物、住院时间>2周是艰难梭菌无症状感染的独立危险因素(P<0.05)。结论 艰难梭菌产毒素量是导致临床是否出现腹泻症状的重要因素;住院时间>2周、使用抑酸剂、2个月内使用头孢菌素类抗菌药物均是艰难梭菌无症状感染的独立危险因素。     

抗艰难梭菌毒素B抗体可以预防艰难梭菌感染复发

正目前已有较多艰难梭菌感染(CDI)复发的危险因素研究,但绝大多数研究没有考虑到患者内源性抗艰难梭菌毒素A、B抗体水平对CDI复发的影响。本文分析一项II期临床试验中安慰剂组CDI患者体内抗艰难梭菌毒素A、B单克隆抗体在防止CDI复发中的作用。有艰难梭菌感染症状并接受甲硝唑和万古霉素治疗的患者被纳入到此研究,     

成人艰难梭菌感染临床实践指南:美国卫生保健流行病学会与感染病学会2010年更新

自1995年美国卫生保健流行病学会(SHEA)确定了艰难梭菌是急性感染性腹泻的主要病原之一以来,艰难梭菌感染(Clostridium difficile infection,CDI)流行病学及治疗发生了显著的变化.艰难梭菌仍然是卫生保健相关腹泻最为重要的病原菌,同时在社区获得性腹泻病原中的重要性也逐渐增加.近年来出现了一种高毒力艰难梭菌菌株,在全球引起更为严重的感染. 已有报道称甲硝唑对重症CDI疗效下降.尽管目前已获得大量的研究数据,有关CDI在许多方面仍然存在争议.本指南对CDI的流行病学、诊断、治疗、感染控制以及环境管理进行了更新.     

ICU腹泻患者艰难梭菌感染分子流行病学特征和危险因素

正艰难梭菌是一种产芽孢专性厌氧革兰阳性杆菌,广泛分布在自然环境中,可在健康人肠道定植。当肠道微生态平衡遭到破坏时,肠道正常菌群受到抑制,艰难梭菌大量生长并释放毒素,引起艰难梭菌感染(Clostridium difficile infection,CDI)。CDI包括艰难梭菌相关性腹泻(Clostridium difficile associated diarrhea,CDAD)和伪膜性肠炎     

TaqMan实时荧光定量PCR检测艰难梭菌

目的 建立特异敏感的实时荧光定量PCR方法,用于艰难梭菌的快速检测;评价基于纯培养艰难梭菌和粪便中艰难梭菌的2种标准曲线;并应用该荧光定量PCR法对急性艰难梭菌感染（CDI）的小鼠进行粪便含菌量检测评价。方法 针对艰难梭菌基因组中16S rRNA序列设计特异性引物和探针,建立一套快速检测艰难梭菌含量的实时荧光定量PCR方法,验证方法的特异性、灵敏性;绘制艰难梭菌纯菌浓度梯度稀释标准曲线和粪便中同浓度梯度艰难梭菌的标准曲线,比较两者的差异;用艰难梭菌高毒株NAP1/027感染用抗生素处理的C57BL/6小鼠,建立CDI小鼠模型,同时应用该荧光定量PCR和活菌培养法定量检测小鼠粪便中的艰难梭菌含量变化。结果 建立的TaqMan实时荧光定量PCR具有较高的灵敏性和特异性,生成标准曲线的相关系数为0.999 8,斜率为-3.400 4;用纯培养艰难梭菌和粪便中艰难梭菌分别制备标准曲线,结果表明2种标准曲线定量检测结果差异无统计学意义。建立CDI小鼠模型,应用该荧光PCR能有效、准确的检测出粪便中艰难梭菌的含量,可替代费时费力的活菌培养计数法。结论 用纯培养艰难梭菌来制备标准曲线不影响对含菌粪便标本的准确定量检测,荧光定量PCR能准确快捷地检测CDI小鼠粪便中的艰难梭菌含量,比活菌计数更快速和方便,可用于艰难梭菌感染小鼠模型中小鼠肠道内艰难梭菌定植的定量检测。     

艰难梭菌感染治疗的最新进展

艰难梭菌是引发传染性结肠炎的主要原因,在住院病人和长期居住在护理机构的病人中尤为普遍。过去十年里,艰难梭菌已越来越成为一个有问题的病原体。增强的毒性、传染性和无效的控制措施使艰难梭菌成为感染的主要原因。艰难梭菌感染（CDI）的历史疗法有着不可接受的高失败率和高复发率。     

艰难梭菌感染实验室诊断的研究进展

艰难梭菌是一种专性厌氧革兰阳性芽孢杆菌,一般认为是环境和人类肠道中的正常菌群。过度应用抗生素、免疫抑制剂或化疗药物使耐药的艰难梭菌产毒株过度繁殖并释放毒素是导致艰难梭菌感染（Clostridioides difficile infection, CDI）的主要因素。CDI的发病率在全球范围内不断增加,尤其是高产毒株在北美地区造成了医院内的暴发流行,引起了世界范围的关注。在此对艰难梭菌的致病机制和实验室诊断方法的研究进展进行阐述,为艰难梭菌相关性腹泻的早期诊断和治疗提供新思路。     

应重视艰难梭菌感染的检测

艰难梭菌(Clostridium difficile)为革兰阳性厌氧产芽孢杆菌,是人类肠道中的正常菌群之一.艰难梭菌本身没有侵袭性,其中部分细菌(产毒株)可通过分泌毒素A、毒素B和(或)二元毒素从而引起抗生素相关性腹泻、结肠炎甚至致死性伪膜性肠炎,统称为艰难梭菌感染(Clostridium di ficile infection,CDI).艰难梭菌为医院获得感染性腹泻最主要的病原菌,在抗生素相关性腹泻病因中艰难梭菌亦占20％～30％;而伪膜性肠炎则几乎100％由艰难梭菌所致.肠道外CDI如败血症等则极为罕见.不仅仅是抗菌药物,其他影响肠道正常菌群平衡、降低艰难梭菌定植抵抗能力的因素,如老年、胃肠道手术、应用抗肿瘤药物、长期住院和免疫功能缺陷等均为CDI的危险因素.     

艰难梭菌感染病原学检测技术

<正>艰难梭菌感染(Clostridiodes dif?cile infection,CDI)是指艰难梭菌引起的感染性疾病,主要表现为腹泻、腹痛、发热等。近年来,CDI的发病率呈逐年上升趋势,表现为复发率,严重程度及病死率增高^[1-2]。2011年美国疾病控制和预防中心流行病学调查发现,艰难梭菌是医疗保健感染最常见的病原体,达到12.1%^[3]。自2000年以来,CDI死亡率也逐年上升,在地方性流行期间为4.5%～5.7%,在大流行期间为6.9%～16.7%^[4]。儿童CDI的发病率总体呈上升趋势,约为13.8例/100000人,71%来自社区感染^[5]。但目前很多医院对CDI的检测手段十分有限,且诊断率不高,     

艰难梭菌感染的实验室诊断技术研究进展

艰难梭菌是一种专性厌氧革兰阳性芽孢杆菌,本身没有侵袭性,但长期使用广谱抗菌药物等因素易导致菌群失调,引起艰难梭菌感染(Clostridium difficile infection,CDI)及相关性腹泻,严重时可出现伪膜性肠炎甚至死亡。误诊或漏诊该菌感染可能延误治疗并增加交叉感染风险,因此,对其快速精准检验尤为重要。检验结果可为CDI的诊断与治疗提供重要依据。该文对CDI实验诊断技术作一综述。     

抗生素相关性腹泻治疗及预防

1引言抗生素相关性腹泻（antibiotic associated diarrhea,AAD）是指伴随抗生素使用而发生的无法用其他原因解释的腹泻〔1〕。对应用抗生素种类不同,成人AAD发病率达5%～25%〔2〕。随着广谱抗生素应用增加,自1950年人们开始关注这类腹泻。AAD严重程度从单纯性腹泻到难辨梭状芽孢杆菌（C.difficile）相关性腹泻以及假膜性结肠炎（PMC）。     

2013年消化系统疾病主要临床进展

2013年,国内外胃肠病学相关学会及专家制订或更新了诸多消化领域的指南及共识意见,无论从涉及的疾病种类之多到更新的范围之大都是近年少有。作者主要从胃轻瘫、慢性胃炎、胃食管反流病、贲门失驰缓症、成人急性感染性腹泻、艰难梭状芽胞杆菌感染、胰腺疾病、炎症性肠病、肝脏疾病等疾病的更新部分入手,全面详实的介绍了消化领域疾病的国内外诊治进展,以期为消化内科医生诊疗疾病提供帮助。     

异基因造血干细胞移植过程中患者艰难梭菌感染与肠道微生态失调关系的临床研究

本研究探讨异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation,allo-HSCT）过程中患者艰难梭菌相关性腹泻（clostridium difficile associated diarrhea,CDAD）与肠道微生态的关系,了解肠道微生态失衡的临床特征,寻找有效防治措施,保护肠道菌群,减少细菌易位及感染的发生。对44例allo-HSCT后腹泻患者采用艰难梭菌毒素A＆B检测试剂盒进行毒素检测,采用厌氧培养方法进行艰难梭菌的分离、鉴定。对患者粪便标本进行肠道微生态研究;采用光冈复合式法对目的菌群（双歧杆菌、乳酸杆菌、类杆菌、消化链球菌、产气荚膜梭菌、肠杆菌、肠球菌、酵母菌）进行定性定量分析。结果表明：44例腹泻患者中共检测出12例艰难梭菌阳性,阳性率为27.27%;CDAD的发生与使用抗生素或化疗药物有关;CDAD患者的肠道微生态发生了明显变化,表现为乳酸杆菌、双歧杆菌、类杆菌、肠杆菌等细菌数量明显下降;对CDAD用万古霉素、甲硝唑等药物并配合给予益生菌治疗效果好,但有一定复发率（16.67%）。结论：allo-HSCT并发CDAD与肠道微生态的改变有关,应用敏感抗生素治疗的同时应积极扶植肠道菌群,这样的治疗有利于改善病情和减少复发。     

艰难梭菌毒素A对K562细胞生长增殖的影响

本研究探讨艰难梭菌毒素A(Tcd A)对人慢性髓系白血病(CML)细胞株K562生长增殖的影响及其机制。采用四氮唑蓝比色法(MTT法)观察Tcd A对K562细胞增殖的抑制作用;流式细胞术分析细胞周期及线粒体膜电位的变化;免疫细胞化学法观察细胞色素C蛋白的表达水平;DNA凝胶电泳技术检测细胞凋亡。结果表明,不同浓度的Tcd A明显抑制K562细胞增殖,呈一定的时间和浓度依赖性;流式细胞仪检测显示,细胞阻滞于G0/G1期,并出现凋亡峰,细胞内细胞色素C蛋白含量增高;DNA凝胶电泳出现片段化的梯形带。结论:Tcd A可以抑制K562细胞的生长增殖,并诱导其凋亡,其机制可能与线粒体膜电位降低,基质中释放出致凋亡活性物质细胞色素C有关。     

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors

Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H⁺/K⁺-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.     

Clostridium difficile: dealing with a silent menace

Clostridium difficile infection is a growing problem and infection is not confined to acute hospitals. People with C. difficile may be cared for in community hospitals or at home. Some people with C. difficile suffer recurrent bouts of infection, others are left with ongoing bowel problems as a result of the infection. Prevention, wherever possible, through prudent antibiotic prescribing and scrupulous infection control procedures can reduce infection risks. Prompt diagnosis and treatment can reduce the risks of life threatening colitis or chronic bowel problems.     

The diagnosis of Clostridium difficile-associated diarrhea: comparison of Triage C. difficile panel,EIA for Tox A/B and cytotoxin assays

This study prospectively compared; Triage(R) C. difficile test (TCT), TechLab C. difficile toxin A-B enzyme immuno-assay (EIA), and cell-culture cytotoxin test (CT). Of the 400 stools tested, 99 were positive by any test with 92, 41 and 58 detected by TCT, EIA and CT, respectively. Culture of discordant samples indicated that 52 contained C. difficile (42 toxigenic, 10 non-toxigenic), 10 contained Clostridium species and 2 had no detectable clostridium isolates. There were 21/42 toxigenic C. difficile isolates from 17 patients whose stools were negative when originally tested by CT. Review of available patient charts indicated that 12/14 did not previously or currently have C. difficile associated diarrhea, whereas 2 patients developed disease within a few days. Compared to CT as the gold standard, the sensitivity and specificity were; 93%, 89% and 66%, 99% for TCT and EIA respectively. The 8 stool samples with Toxin A(-) Toxin B(+) isolates were detected in 8, 4, and 6 samples by TCT, EIA and CT, respectively. In summary, TCT as a screening test allowed reliable reporting for 85% of stools on the day of receipt. For the 15% of stools requiring further testing we recommend the use of CT.     

Leukemoid reaction due to Clostridium dificile infection in acquired immunodeficiency syndrome: two case reports and a review of the literature

The clinical presentation of colitis associated with Clostridium difficile infection in immunosuppressed patients with acquired immunodeficiency syndrome (AIDS) has not been completely characterized. Previous reports suggest that these patients present with low blood leukocyte counts, consistent with the impaired myelopoiesis that can occur with human immunodeficiency virus (HIV) infection. In contrast, we describe the cases of two patients with colitis associated with C difficile infection who developed intense leukemoid reactions despite being in advanced stages of AIDS. To the best of our knowledge, these are the first described cases of leukemoid reaction associated with C difficile or other bacterial infection in AIDS patients. We review the literature on C difficile colitis in patients infected with HIV and suggest that severe C difficile infection should be considered in such patients presenting with leukemoid reaction and diarrhea.     

Probiotics for Clostridium difficile diarrhea: putting it into perspective

Clostridium difficile diarrhea is an expensive, life-threatening infection associated with serious morbidity and mortality, even among previously healthy individuals. Relapses from the infection are common following standard antibiotic treatments, with 3-5% of patients who contract C. difficile diarrhea unable to discontinue vancomycin due to continual relapses. Such patients may have a focal immunodeficiency in which they fail to mount an immune response against C. difficile. For these individuals, antimicrobial therapies are unable to eradicate the microorganism because no antibiotics are capable of killing C. difficile spores. Although they are considered alternative medicine, probiotics have provided a safe and effective means of restoring gastrointestinal flora and alleviating diarrhea, particularly for individuals experiencing multiple relapses.     

我国艰难梭菌流行特征和研究进展

艰难梭菌被认为是抗生素和医疗机构相关性腹泻的主要病原,被美国疾病预防控制中心列为抗生素相关的紧迫公共卫生威胁之一。 近10年来,我国艰难梭菌感染的发生率显著上升,艰难梭菌的研究也日益深入,本研究旨在结合已有报道和研究成果,对我国艰难梭菌的流行特征进行总结,并展望领域内的热点问题,以期对未来研究提供参考。