临床微生物标本采集与检测

这个腹泻病人，您考虑是感染吗？什么病原体引起？

A67-year-old man presented with fever, abdominalcramping, and frequentdiarrhea (six to nine bowel movements per day)for 4 days.Three weeks before the current episode, he had undergonea hip replacement and was rehabilitating in an orthopedic unit. During thathospitalization, he developed anosocomial pneumonia and was treatedempirically withcefuroxime andclindamycin. He graduallyimproved and was discharged a week before his current presentation, withmaintenance oral antibiotics, to recuperate at home. His wife hadno similarsymptoms.【google翻译】一位67岁的男子出现发烧，腹部绞痛，腹泻频繁（六至九次每天排便）4天。当前事件的前三个星期，他已经经历了髋关节置换术，并在骨科单元恢复。在住院期间，他并发了院内获得性肺炎，经验性治疗头孢呋辛和克林霉素。他逐渐好转，在出现当前状况前一个星期出院，维护口服抗生素，在家休养。他的妻子有没有类似的症状。PHYSICALEXAMINATION VS: T39°C, P 114 /min, R 18/min, BP 94/50 mmHgPE: The patient appeared confused and very pale. He could not answer questions abouthis current condition. His skin showed decreasedturgor, and hisoralmucosa wasdry.

【google翻译】体检

VS：T39°C，P114/分，R18/min，血压94/50毫米汞柱PE：患者出现困惑，非常苍白。他不能回答关于他目前的状况。他的皮肤呈膨压下降，和他的口腔黏膜干燥。

LABORATORYSTUDIESBloodHematocrit: 45%WBC: 12,800/μLDifferential: 71% PMNs, 24% lymphsBlood gases: NormalSerum chemistries: BUN 28 mg/dL, creatinine 1.5 mg/dL

【google翻译】实验室研究血：红细胞比容值45％WBC：12,800/μL，分类：71％的中性粒细胞，24％lymphs血气：正常血清生化检查：尿素氮28毫克/升，肌酐1.5毫克/升

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icchina&&

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ImagingSigmoidoscopy revealed erythematous and friable colonicmucosa.DiagnosticWork-UpTable 1 lists the likely causes of illness (differentialdiagnosis). A clinical diagnosis of antibiotic-associated diarrhea or colitiswas considered based on diarrhea (more than five bowel movements per day),remarkable sigmoidoscopy, and exposure to antibiotics.Detection of toxinsin the diarrheal stool is the mainstay of delineation of the etiology.

【google翻译】

成像

乙状结肠镜检查发现结肠黏膜红斑和易碎。

诊断工作

表1 列出的可能原因疾病的鉴别诊断。被认为是抗生素相关性腹泻或结肠炎临床诊断为腹泻（超过五每天排便），显着的乙状结肠镜检查，并暴露于抗生素的基础上。检测腹泻粪便中的毒素是主体圈定的病因。

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是否是抗生素相关性腹泻？伪膜性肠炎？或者是艰难梭菌感染？

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TABLE 1 Differential Diagnosis and Rationale for Inclusion (consideration)

Antibiotic-associated diarrhea or colitis (Clostridium difficile)

Bacterial enteritis (dysentery)

Campylobacter

Salmonellosis

Inflammatory bowel disease (IBD)

Irritable bowel syndrome (IBS)

Viral gastroenteritis

表1 鉴别诊断和并入的理由（考虑）抗生素相关性腹泻或结肠炎（难辨梭状芽孢杆菌）

细菌性肠炎（痢疾）

空肠弯曲菌

沙门氏菌病

炎症性肠病（IBD）

肠易激综合征（IBS）

病毒性肠胃炎

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Rationale: Diarrhea has multiple etiologies, and specific clues are usually necessary in addition to microbiologic studies to determine a precise etiology. Prior antibiotic use is commonly associated with C. difficile. Bacterial and viral causes are certainly possible, but they are difficult to distinguish. Noninfectious causes, such as IBD and IBS, are somewhat less likely to manifest in the elderly but are also important to consider. Noninfectious causes are often associated with recurrent symptoms and not necessarily a single episode.

【google】

理由：腹泻有多种病因，除了微生物学研究，以确定确切病因通常是必要的具体线索。之前使用抗生素通常与难辨梭状芽孢杆菌。细菌和病毒的原因当然是可能的，但他们是很难区分。非感染性的原因，如IBD和IBS，不太可能体现在老人，但也是很重要的考虑。非感染性的原因往往与复发症状，而不一定是一个单一的情节。

icchina&&

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COURSE

A stool specimen was sent to the laboratory, which within 24 hours yielded a positive test for a toxin.

ETIOLOGY

Clostridium difficile-associated diarrhea (CDAD)

MICROBIOLOGIC PROPERTIES

C. difficile is a strictly anaerobic bacterium. The organisms are Gram-positive, spore-forming rods. Toxigenesis is an important property of diarrheagenic C. difficile. These strains produce two exotoxins: toxin A and toxin B, which can be detected by ELISA (sensitive, specific, and simple).

【google翻译】

课程

粪便标本被送往实验室，在24小时内报告毒素阳性的检测结果。

病因

艰难梭菌相关性腹泻（CDAD）

微生物特性

难辨梭状芽孢杆菌是一种严格的厌氧细菌。微生物是革兰氏阳性，形成孢子的杆菌。产毒素是致泻的难辨梭状芽孢杆菌是一个重要的特点。这些菌株产生的外毒素：毒素A和毒素B，它可以通过ELISA检测（敏感，特异，简单）。

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路过学习

icchina&&

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EPIDEMIOLOGY

C. difficile is carried asymptomatically as part of the large intestinal flora of 50% of all healthy neonates during the first year of life. The carriage rate decreases to less than 4% in adults. This rate remains constant in the population. Among hospitalized adults who have received antibiotic therapy, carriage rates may be as high as 46% (particularly during outbreaks). The primary (index) cases occur via endogenous mode in precolonized patients exposed to antibiotics. Secondary cases occur via exogenous transmission of spores in the hospital environment and by the hands of health care attendants, causing nosocomial outbreaks. Antimicrobial agents of all classes and several anticancer chemotherapeutic agents have been incriminated as inciting agents of CDAD. The most commonly incriminated antimicrobial agents are clindamycin, cephalosporins, and ampicillin.

CDAD is toxin mediated. C. difficile is ordinarily suppressed by the normal colonic flora, preventing overgrowth. Broad-spectrum antibiotics suppress normal flora. Clindamycin, which inhibits growth or kills many different species of anaerobic bacteria in the colon, does not suppress C. difficile. The overgrowing vegetative organisms of C. difficile produce at least two toxins: toxin A and toxin B. Both toxins appear to act by the same mechanism, but toxin B is more potent. Both toxins exert their effects by binding to cellular GTP-binding proteins (in the Rho family within target cells). The toxins inactivate these proteins by glycosylation, dysregulating the action of the cytoskeleton in epithelial cells of the colonic mucosa, and causing depolymerization of actin. Break-up of actin filaments causes profound cytopathic effect, damaging the cellular lining of the bowel wall and causing erythematous and friable colonic mucosa, ulceration, and hemorrhagic necrosis.

【google翻译】

流行病学

难辨梭状芽孢杆菌进行无症状， 50％的所有健康的新生儿在生命的第一年的大肠道菌群的一部分。载运率下降至不到4 ％，在****。这在人口率保持不变。在住院的****已接受抗生素治疗，携带率可能高达46％（尤其是在爆发）。主（指数）的情况下发生的通过暴露于抗生素precolonized患者的内生模式。继发病例发生在医院环境和健康护理员手中的孢子通过外源性传播，引起院内爆发。所有类和一些抗癌化疗药物的抗菌药物已经牵连CDAD煽动剂。连累最常用的抗微生物剂是氯林可霉素，头孢菌素和氨苄青霉素。

CDAD毒素介导的。难辨梭状芽孢杆菌通常会抑制正常的结肠菌群，防止过度生长。广谱抗生素抑制正常菌群。克林霉素增长，从而抑制或杀死许多不同种类的厌氧菌在结肠，不抑制难辨梭状芽孢杆菌。难辨梭状芽孢杆菌的营养生物过快产生至少两种毒素：毒素A和毒素B.这两种毒素出现相同的机制，但毒素B是更有效的。这两种毒素发挥其功效，结合蜂窝GTP结合蛋白（在靶细胞内的Rho家族）。毒素灭活这些蛋白质的糖基化， dysregulating结肠黏膜上皮细胞中的细胞骨架的作用，引起的肌动蛋白的解聚。微丝分手导致深刻的细胞病变效应，破坏细胞衬里的肠壁，引起红斑和易碎的结肠黏膜，溃疡，出血性坏死。

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l路过学习了。好复杂啊！

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TREATMENT

Treatment of CDAD begins with discontinuation of the offending agent and implementation of any necessary supportive measures. The preferred oral antimicrobial agent is metronidazole. The oral metronidazole therapy should be begun as soon as possible. Oral vancomycin is an alternative, but its use carries the risk of emergence of vancomycin-resistant enterococci and colonization, which may pose serious health risks. In addition, it is much more expensive. Relapse is common because C. difficile spores are resistant to many antibiotics, and continued antibiotic use can delay the return of normal flora that would inhibit growth of C. difficile.

NOTE

Pseudomembranous colitis, a complication of CDAD, occurs in untreated acute cases and is characterized by multiple elevated, yellowish white plaques (pseudomembranes) within the colon. Toxic megacolon is a serious sequela of pseudomembranous colitis and may lead to sepsis due to perforation and polymicrobial infection of colonic flora.

【google翻译】

治疗

治疗CDAD开始停止违规代理任何必要的配套措施和实施。优选的口服抗菌剂是甲硝唑。口服甲硝唑治疗应尽早开始。口服万古霉素是一种替代方法，但它的使用进行风险出现耐万古霉素肠球菌和殖民统治，这可能会造成严重的健康风险。此外，它是昂贵得多。复发是很常见的，因为难辨梭状芽孢杆菌孢子对多种抗生素耐药，抗生素的使用能延缓返回正常菌群，抑制难辨梭状芽孢杆菌的生长。

注意

CDAD ，伪膜性结肠炎的并发症发生在未经治疗的急性病例的特点是多个高架，黄白色斑块（假膜）结肠内。中毒性巨结肠伪膜性肠炎，是一种严重的后遗症，可能导致败血症，由于穿孔结肠菌群感染和幼童。

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OUTCOME

Specific antibiotic treatment for pneumonia was tapered off, and specific treatment for CDAD was begun with oral metronidazole in addition to hydration. The patient became afebrile within 36 hours, and his diarrhea resolved after 3 days. He was able to return home without any further problem and had no further episodes of diarrhea.

结局

特定抗生素治疗肺炎逐渐减少，具体的治疗CDAD开始口服甲硝唑除了水化。成为发热病人在36小时内，他的腹泻后3天内解决。他能够回国，而任何进一步的问题，并没有进一步的腹泻发作。

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PREVENTION

Limiting use of broad-spectrum antibiotics is an important measure in reducing the risk of developing C. difficile colitis. Measures to control the spread of infection within the hospital include hand washing, removing gloves before attending another patient, enteric precautions, and isolating the index case or cohort patients with CDAD.

预防

限制使用广谱抗生素，是减少发展艰难梭菌结肠炎的风险的一项重要举措。控制医院内感染扩散的措施包括洗手，脱手套在出席另一个病人之前，肠道的预防措施，以及索引的情况下或队列CDAD患者隔离。