1、Measures to Control and Prevent Clostridium difficile Infection,Clinical Infectious Diseases 2008,难辨梭状芽孢杆菌,革兰阳性专性厌氧菌，产芽孢为正常人固有菌群的组成部分，约占3%1025的抗生素相关性腹泻和几乎所有的伪膜性肠炎均由难辨梭菌引起芽孢耐干燥，在空气中存活长达5个月，产芽孢是难辨梭菌造成爆发性感染的主要原因,难辨梭状芽孢杆菌,主要致病的毒素为A毒素及B毒素A毒素：肠毒素，其与肠黏膜受体结合，引起肠上皮细胞骨架结构改变，使细胞间紧密连结的通透性及血管通透性增加，从而产生一系列临床症状B毒素
2、：细胞毒素，可产生细胞毒作用而损害肠黏膜二元毒素CDT（部分菌株，5%-6%）是导致难辨梭菌相关腹泻发病率和严重性增加的可能原因,Clostridium difficile infection (CDI),CDI是院内感染的重要组成部分临床表现腹泻：稀水样便，糊状便、黏液便、脓血便，有时有膜状漂浮物腹痛、腹胀毒血症：发热、谵望、定向力障碍等，严重者发生低血压、休克、严重脱水、电解质紊乱及代谢性酸中毒，甚至急性肾功能不全。,并发症中毒性巨结肠麻痹性肠梗阻肠穿孔CDI的发生与抗生素的应用密切相关,CDI rates: in the United States have tripled from 2
3、000 to 2005There is a need for more-effective infection control and prevention measures to reduce CDI incidence and disease severity.,感染传播过程,传染源：感染患者及带菌者,易感者,传播途径,环境及传播媒介,Infection control measures,preventing ingestion of the organism and its spores by patients: the environment personnel hygiene bar
4、rier methodsreducing the chance of developing CDI in the event of such ingestion: good antimicrobial stewardship,the environment,环境污染是造成疾病传播的重要因素Among patients whose prior room occupant was MRSA positive, 3.9% acquired MRSA, compared with 2.9% of patients whose prior room occupant was MRSA negative
5、(adjusted odds ratio, 1.4; P = .04). VRE, Among patients whose prior room occupant was VRE positive, these values were 4.5% and 2.8% respectively (adjusted odds ratio, 1.4; P = .02),Arch Intern Med 2006,消毒剂的选择,常用消毒剂 季铵盐类消毒剂含酒精消毒剂戊二醛环氧乙烷84及其他含氯消毒剂过氧化氢,含氯消毒剂,在CDI高发病房，与季铵盐溶液相比应用1：10的次氯酸钠消毒溶液能有效减少难辨梭菌的环
6、境污染并降低CDI的发病率,Mayfield. Clin Infect Dis 2000Apisarnthanarak, Mayfield JL. Clin Infect Dis 2004,高浓度(10%)次氯酸钠有恶臭，且长时间使用对各种设备具有腐蚀性并且可能导致呼吸困难CDC推荐在CDI暴发流行时使用漂白剂（次氯酸钠）,消毒区域的选择,The heaviest contamination is found on floors and bedrails; windowsills, commodes, toilets, bedsheets, call buttons, scales, bloo
7、d pressure cuffs, electronic thermometers, flow-control devices for intravenous catheters, and feeding tube equipment,手部卫生,手传播媒介It has been shown that as levels of environmental contamination increase, so does the prevalence of C. difficile hand carriage among health care workers,Am J Med 1996,手部卫生,
8、快速手消毒剂（含酒精消毒剂）洗手手套的使用,手部卫生,the most effective way to remove them from hands is through handwashingglove use is the precaution proven to be most effective in preventing the transmission of C. difficile during care of a patient with CDI it is a viable precaution to use gown,快速手消毒剂（含酒精消毒剂）A recent stud
9、y found that the reduction in spore counts after applying any of 3 alcohol-based hand gels was significantly lower than after handwashing with chlorhexidine gluconate (P .009). A mean of 30% of the inoculum of C. difficile spores remaining on contaminated hands after the use of alcohol-based gel was
10、 transferred to a second volunteer by handshaking 20,Leischner J. 2005,A recent study at a US hospital found that, although there was a progressive increase from 10% to 85% in the use of alcohol-based hand rubs over a 3-year period (P 0.001), there was no evidence of an increase in the incidence of
11、CDI,Johnson S. Am J Med 1990,Compliance with hand hygiene practices has dramatically improved since the introduction of alcohol-based hand sanitizers, which effectively decontaminate health care workers hands by eliminating nonspore-forming bacteria.Use of alcohol-based hand rubs should be widely pr
12、omoted,Additional measures,仪器、设备的消毒（强碱性戊二醛、环氧乙烷）：显微镜等尽量选用一次性物品：如体温计对使用后物品的消毒处理：呼叫器、床栏、静脉输液系统、泵等在对病人进行治疗、护理时戴手套可以明显降低CDI发病率；隔离衣仍推荐使用尽早识别及报告难辨梭菌感染患者：电子报警设备隔离: 疑似及确诊患者分病房，分区域收治,防止CDI爆发的策略,快速识别、报告及隔离CDI患者感染及疑似病人的标记、隔离治疗接触防护及病房消毒：穿隔离衣、戴手套及手部卫生、使用次氯酸钠消毒确定解除隔离的标准：CDC推荐在恢复正常大便习惯后解除隔离教育，对手部卫生及隔离措施的依从性：匹兹堡的爆发
13、流行,ANTIMICROBIAL STEWARDSHIP,抗生素，尤其是克林霉素及二、三代头孢菌素的使用与CDI的发生密切相关应用广谱抗生素的患者是否应预防性应用口服甲硝唑或万古霉素？,应用任何抗生素都会增加患者患CDI的风险，并且可能增加日后CDI的复发风险，甲硝唑或万古霉素的应用也可能增加患者发生CDI的风险并且万古霉素的使用会诱发耐万古霉素细菌的产生,因此，对应用广谱抗生素的患者不建议预防性应用口服甲硝唑或万古霉素,无症状携带者与健康人相比发生CDI的几率相同，但无症状携带者作为院内感染重要的传染源，会增加医院内CDI的发病率应用甲硝唑或万古霉素是否会降低CDI的发病率呢？,四项研究,1
14、项前瞻性研究：在所有难辨梭菌携带者中应用万古霉素后CDI的发病率可由16.6%降至3.6%（Eur J Clin Microbiol 1987）2项非对照研究结果表明对无症状携带者的治疗并没有降低CDI的发病率（Am J Infect Control 1990; Lancet 1986）,1项随机安慰剂对照的研究：30例无症状携带者随机分为3组，分别口服万古霉素（250mg Q6h）、灭滴灵（500mg Q12h）、安慰剂（Q8h）共10天，实验结束即刻三组的带菌率分别为10%、70%、80% ，但万古霉素组中9例转阴的患者在20天左右后又复转阳，并且在2个月的随访期末，万古霉素组6/9的患者
15、培养阳性，且1人发展为CDI ，而安慰剂组仅为2/10(P .05)培养阳性,根据以上有限的实验证据，不建议对无症状带菌者进行治疗,OTHER MANAGEMENT ISSUES,抑酸治疗胃酸，天然的杀菌剂抑酸治疗是抗生素相关性腹泻的危险因素抑酸治疗是否会增加CDI发生率还存在争议支持CMAJ 2004; JAMA 2005; CMAJ 2006反对Clin Infect Dis 2006; N Engl J Med 2005,OTHER MANAGEMENT ISSUES,胃管/鼻饲的使用一项前瞻性队列研究显示：管饲是CDI的独立危险因素(OR, 3.1; 95% CI, 1.18.7; P
16、.03)预防措施：手套的使用,CONCLUSION,Effective measures are available to reduce environmental contamination with C. difficile and to prevent the spread of this pathogen by workers and equipmentCompliance with enhanced environmental cleaning and contact precautions must be closely monitoredEnhance antimicrobial stewardship are part of the multifaceted interventions to prevent CDI,
