艰难梭菌感染流行病学特征、实验室诊断与治疗的研究进展

艰难梭菌(Clostridium difficile)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。近年来该菌引起的医院内感染日益增多,是医院内获得性腹泻的主要病原菌。抗菌药物的过度应用被认为是引起艰难梭菌感染(Clostridium difficile infection,CDI)发病率增加的主要因素。CDI的发病率在全球范围内不断增加,尤其是新型高产毒株在北美地区造成了医院内感染的暴发流行,引起了世界范围的关注。本文对CDI的流行病学特征、致病机制、实验室诊断、治疗以及感染控制等方面的最新研究进展进行阐述,旨在为CDI的早期预防提供新思路。     

艰难梭菌耐药性及其机制研究进展

正性厌氧菌,广泛存在于自然环境中,常见于动物和人体肠道中,艰难梭菌属于人体肠道的正常菌群。艰难梭菌感染(CDI)是由产毒株艰难梭菌过度繁殖导致肠道菌群失调并释放毒素引起的,被认为是干扰粪便微生物群的直接结果,导致艰难梭菌和毒素表达的过度生长。这与抗生素的使用密切相关。但是,其他几种危险因素也与CDI的发展有关,包括胃酸抑制,高龄,医院暴露以及细胞或体液免疫功能低下[1]。主要临床症状为发热、腹痛、水样便腹泻[2]。自2002年起发达国家如欧洲、美国等地区多次     

艰难梭菌感染实验室诊断方法的研究进展

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.长期应用抗生素、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相关性腹泻(CDAD)的主要因素.CDAD的发病率在全球范围内不断上升,尤其是高产毒株在北美地区引起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CDAD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.     

艰难梭菌感染的流行病学及危险因素

艰难梭菌(Clostridium difficile,CD)是一种寄生于肠道的革兰阳性梭状芽孢杆菌。随着抗生素的广泛应用,艰难梭菌感染（Clostridium difficile infection,CDI）的发病率在全球范围内逐年升高。尤其是CD高产毒株（BI/NAP1/027/毒素Ⅲ型）的出现和流行,使得CD成为近年来医疗卫生相关的重要病原菌之一。目前,国内外有关CDI流行病学方面的研究不断更新。本文对CDI的流行病学情况及危险因素进行综述,旨在提高临床医务工作者对CDI的认识。     

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.     

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。     

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,     

艰难梭菌感染：一种新的威胁

艰难梭菌是住院患者抗生素相关性腹泻的重要病因。近年来,由于艰难梭菌高毒力株的出现,导致感染人数明显增多,疾病严重程度增加,已成为一种新的威胁。艰难梭菌感染（clostridium difficile infection,CDI）的诊断应结合临床表现和实验室检查两方面。合理使用抗菌药物是减少CDI最根本有效的方法,另外,应加强院内感染控制措施以控制感染的传播。     

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。     

艰难梭菌感染的预防及疫苗研究进展

艰难梭菌是抗生素相关性腹泻及伪膜性肠炎等医院获得性感染性疾病的主要病原菌。近些年高致病性BI/NAP1/027核糖体分型成为流行菌株,时常出现感染爆发流行,复发率及病死率呈上升趋势,造成极大的人力、财力、物力损失。因此,重视起艰难梭菌感控是必要的。疫苗研究是防治艰难梭菌的重要手段,国外研制艰难梭菌疫苗近20年,取得了一定进展。本文将对艰难梭菌预防及疫苗研究现状进行总结,期望能为临床医师和科研人员提供参考。     

Fidaxomicin: first-in-class macrocyclic antibiotic

The incidence of Clostridium difficile has doubled over the past 15 years, and rising mortality rates associated with this infection have followed in its wake. C. difficile infection (CDI) has supplanted methicillin-resistant Staphylococcus aureus as the major cause of nosocomial infection. An insufficient response rate to currently available CDI therapies has prompted the search for new and alternative treatment modalities for this disease. The investigational pipeline includes evaluation of new antimicrobial agents that exhibit good activity against C. difficile without altering normal gut flora, C. difficile toxin-absorbing compounds, and preformed antibodies and vaccines against C. difficile toxin. In two robust clinical trials comparing fidaxomicin to vancomycin in the treatment of CDI, treatment with fidaxomicin demonstrated a superior global cure (cure without recurrence) rate compared with the current gold standard, vancomycin. Fidaxomicin, the first of a new class of macrocyclic antimicrobial agents, represents an advance in the management of CDI.     

Clostridium difficile infection in cancer patients and hematopoietic stem cell transplant recipients

Clostridium difficile has become the most common bacterial cause of nosocomial diarrhea. High rates of C. difficile infection (CDI) coupled with increasing morbidity and mortality attributed to CDI have sparked a renewed interest in this disease. Emergence of hypervirulent strains, rising rates of severe and recurrent infection and associated infection control challenges, and diagnostic and therapeutic dilemmas are major issues in the non-oncology population. Scant data on CDI exist in the cancer/transplant population. The purpose of this article is to describe the epidemiology, pathogenesis and management of CDI in patients receiving cancer chemotherapeutic agents, and in hematopoietic stem cell transplant recipients.     

Clostridium difficile infection in patients with cancer

Patients with cancer undergoing chemotherapy often have diarrhea, which may result from their treatment or Clostridium difficile infection (CDI). CDI diarrhea is an important diagnosis that can be missed if nurses are not vigilant in their assessments. Treatment for CDI diarrhea is different than that of chemotherapy- or radiation-induced diarrhea. If CDI diarrhea is not treated, it can become life threatening in some patients.     

儿童艰难梭菌感染现状和预防措施

艰难梭菌（Clostridium difficile,CD）是造成院内感染和抗生素相关性腹泻最重要的病原,由于广谱抗生素的大量使用,使得CD感染(CDI)发病率在全球范围内呈上升趋势,成为严重的公共卫生问题。目前虽没有中国儿童CD的流行病学研究数据,但国内儿童疾病诊治过程中存在较为严重的抗生素滥用、且临床对其认识不足,CDI发病率可能比国外更高。本文从CD致病机制、流行现状、危险因素和预防措施等方面进行介绍,以期为防控CDI提供依据。     

Efficacy of LFF571 in a hamster model of Clostridium difficile infection

LFF571 is a novel semisynthetic thiopeptide antibiotic with potent activity against a variety of Gram-positive pathogens, including Clostridium difficile. In vivo efficacy of LFF571 was compared to vancomycin in a hamster model of C. difficile infection (CDI). Infection was induced in Golden Syrian hamsters using a toxigenic strain of C. difficile. Treatment started 24 h postinfection and consisted of saline, vancomycin, or LFF571. Cox regression was used to analyze survival data from a cohort of animals evaluated across seven serial experimental groups treated with vancomycin at 20 mg/kg, LFF571 at 5 mg/kg, or vehicle alone. Survival was right censored; animals were not observed beyond day 21. At death or end of study, cecal contents were tested for C. difficile toxins A and B. In summary, the data showed that 5 mg/kg LFF571 decreased the risk of death by 79% (P < 0.0001) and 69% (P = 0.0022) compared with saline and 20 mg/kg vancomycin, respectively. Further analysis of the pooled data indicated that the survival benefit of LFF571 treatment at 5 mg/kg compared to vancomycin at 20 mg/kg was due primarily to a decrease in the risk of recurrence after end of treatment. Animals successfully treated with LFF571 or vancomycin had no detectable C. difficile toxin. Overall, LFF571 was more efficacious at the end of the study, at a lower dose, and with fewer recurrences, than vancomycin in the hamster model of CDI. LFF571 is being assessed in humans for safety and efficacy in the treatment of C. difficile infections.     

Effects of piperacillin/tazobactam on Clostridium difficile growth and toxin production in a human gut model

OBJECTIVES: Clostridium difficile infection (CDI) is a major cause of morbidity in the nosocomial environment. Antimicrobial agents such as the third-generation cephalosporins, lincosamides and aminopenicillins are well known for their propensity to induce CDI, but the definitive reasons why remain to be elucidated. Despite their broad spectrum of activity against both aerobic and anaerobic bacteria, the ureidopenicillins remain a class of antimicrobials infrequently associated with the development of CDI. METHODS: We used a triple-stage chemostat model that simulates the human gut to study the effects of the ureidopenicillin/beta-lactamase inhibitor combination piperacillin/tazobactam on gut bacterial populations and C. difficile. RESULTS: Piperacillin/tazobactam rapidly reduced all enumerated gut bacterial populations (including bacteroides, bifidobacteria and lactobacilli) below the limits of detection by the end of the piperacillin/tazobactam instillation period. Despite such widespread disruption of gut bacterial populations, C. difficile populations remained principally as spores, with no sustained proliferation or high-level cytotoxin production observed. CONCLUSIONS: Factors other than reduced colonization resistance must be responsible for determining whether CDI develops following antimicrobial administration. We believe the gut model is a promising approach for the study of C. difficile pathogenesis reflecting in vivo events likely to occur in CDI.     

艰难梭菌医院感染管理:监测与防控

近年来,全球艰难梭菌感染（CDI）的发病率不断上升, 实施有效的监测是控制CDI发生和传播的关键。 CDI监测的内容主要包括病例定义、标准化诊断、病例来源定义、CDI的发病情况以及防控建议。 本综述总结有效的CDI监测的关键组成部分,并提供一些切实可行的防控建议,有助于国家及医院进行标准化监测和防控。