Background
Clostridium difficile is the most common identified cause of infectious diarrhea in health care settings and causes 20%-30% of antibiotic-associated diarrhea. The Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America recently published an updated guideline to improve the diagnosis and management of this common and costly nosocomial condition.
Conclusions
C. difficile infection (CDI) has been a common comorbidity in hospital and residential care patients for decades, but the incidence and virulence have increased with the emergence of the NAP1/BI/027 strain as a common entity in Canada and the United States since 2001. This strain has been associated with infection in patients considered “at risk” as well as in nontraditional risk groups, including healthy peripartum women and community-dwelling individuals without recent health care contact.
Risk factors for C. difficile disease include age over 64 years, prolonged hospitalization, exposure to antimicrobials (multiple antibiotics and longer courses increase risk), cancer chemotherapy, HIV infection, and gastrointestinal tract procedures. Whether or not acid-suppressing medication is a risk factor is controversial.
In a recent study, more than 85% of patients with CDI had received antibiotics in the 28 days prior to illness.
Toxigenic culture is the most sensitive test to diagnose C. difficile colitis, but the requisite delay for this method makes the best diagnostic strategy uncertain. The combination of clinical criteria plus a cell cytotoxin assay is most useful in clinical management, and culture and typing are useful for epidemiologic study.
Expert opinion supports patient age, serum creatinine level, and white blood cell count to stratify the severity of CDI.
C. difficile spores are highly resistant to killing by alcohol; studies to date do not demonstrate an increase in CDI with the use of alcohol-based hand gels, but they also do not show a decrease. There are conflicting data on the effects of chlorhexidine hand wash vs. soap on C. difficile hand carriage.
Implementation
Chlorine-based (or other sporicidal) cleaners are recommended for decontamination of areas with elevated CDI rates; however, routine environmental screening is not recommended.
Minimizing the frequency, duration, and number of antibiotics prescribed is important to reduce the risk of CDI. Antimicrobial stewardship, specifically reduction in clindamycin and cephalosporin use, may help reduce the number of C. difficile infections. Although fluoroquinolone use is associated with NAP1/BI/027 C. difficile infection, there is insufficient evidence to recommend restriction of specific drugs within this class or this class of antibiotics.
Probiotics are not recommended for prevention of primary C. difficile infection.
Identification and/or testing of asymptomatic carriers of C. difficile is not recommended, as treatment of these patients is ineffective.
Empiric treatment without testing (where testing is available) is not recommended, since only about 30% of hospitalized patients with antibiotic-associated diarrhea will have CDI.
Testing for C. difficile (culture or toxin assay) should be performed only on diarrheal stool unless an ileus due to C. difficile is suspected.
Repeated C. difficile testing during the same diarrheal illness is not recommended.
Strict hand hygiene, gloves, gowns, and contact precautions in a private room are recommended for the duration of diarrhea in patients with CDI.
Initiation of empiric treatment for CDI pending stool toxin assay is appropriate when severe or complicated colitis is suspected. Treatment must be individualized in cases in which the stool toxin assay is negative.
Antibiotics associated with the development of CDI should be discontinued as soon as possible because their continuation may increase the risk of recurrence. Antiperistaltic medications should be avoided if possible.
Metronidazole (500 mg orally three times daily) is recommended for the initial episode of mild or moderate CDI; vancomycin (125 mg orally four times daily) is recommended for an initial severe episode. Treatment duration should be 10-14 days. CDI complicated by hypotension, ileus, or megacolon should be treated with high-dose vancomycin orally (and rectally as a retention enema in patients with an ileus) with or without intravenous metronidazole.
Subtotal colectomy with preservation of the rectum should be considered for severely ill patients with megacolon, sepsis, or bowel perforation. Serum lactate and leukocyte counts can be useful in stratifying the decision for surgery.
Based on historical data, up to 25% of patients treated for CDI have at least one recurrent episode; this rate is higher in patients over 65 years treated with metronidazole. Treatment of first recurrence of CDI usually is with the same agent as the initial episode; however, management based on disease severity should be stratified as for the initial episode.
Metronidazole should not be used beyond the initial recurrence or for long-term therapy. Second or later recurrences should be treated with vancomycin using a tapered or pulsed schedule.
Reference
Cohen S.H., et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect. Control Hosp. Epidemiol. 2010;31:431-55.
Dr. Golden and Dr. Hopkins write the “The Effective Physician” column, which regularly appears in Internal Medicine News, an Elsevier publication. Dr. Golden is professor of medicine and public health, and Dr. Hopkins is program director for the internal medicine/pediatrics combined residency program at the University of Arkansas, Little Rock.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
背景
难辨梭状芽孢杆菌是医疗保健机构中感染性腹泻的最常见病因，在抗生素相关的腹泻中有20%~30%系该菌所致。美国传染病学会和美国医疗保健流行病学学会近期出版了最新指南，旨在提高对这种常见的、费用不菲的院内感染的诊断和管理。
结论
数十年来，难辨梭状芽孢杆菌感染(CDI)一直是住院患者和护理院患者的一个常见合并症，但随着NAP1/BI/027 菌株的出现，其发病率和毒力也有所增加；该菌株自从2001年起就是加拿大和美国的常见致病菌。此菌株与被视为“有危险”的患者以及非传统危险人群发生感染有关，其中包括健康的围产期妇女和近期未进行医疗保健的社区居民。
难辨梭状芽孢杆菌感染的危险因素包括：年龄在60岁以上、长期住院、应用抗菌药物(联用多种抗生素和疗程较长均会增加风险)、癌症化疗、HIV感染和消化道手术。对于抑酸药物是否是危险因素尚存争议。
近期一项研究显示，85%以上的CDI患者在发病前的28天内接受过抗生素治疗。
产毒菌株培养是诊断难辨梭状芽孢杆菌感染最敏感的检查，但该检查无法立即得出结果，故难以将其视为最佳诊断策略。临床诊断标准结合细胞毒素检测对于临床治疗最具意义，而培养和分型则有助于进行流行病学研究。
专家观点支持利用患者年龄、血肌酐水平和白细胞计数对CDI的严重程度进行分层。
难辨梭状芽孢杆菌芽孢对酒精具有很强的耐受能力；迄今为止，没有一项研究证实应用酒精性洁手凝胶会伴发CDI增加，但是也没有结果表明CDI减少。在洗必泰洗手液与肥皂对手部难辨梭状芽孢杆菌感染的影响方面尚无统一的数据。
实施
现推荐使用以氯为主(或其他杀芽孢性)的清洁剂对CDI高发区进行消毒；但不推荐用于常规的环境筛查。
最大限度地减少处方抗生素的使用频率、疗程及数量对于降低CDI风险很重要。抗菌药物的监督管理，尤其是减少林可霉素和头孢菌素的应用，可能有助于减少CDI的发生。尽管氟喹诺酮的应用与NAP1/BI/027难辨梭状芽孢杆菌感染有关，但也没有充分的证据支持限制这类抗生素中某些特定药物或这类抗生素的使用。
不推荐将益生菌用于原发性难辨梭状芽孢杆菌感染的预防性治疗。
不推荐对无症状难辨梭状芽孢杆菌携带者进行识别和(或)检测，因为没有针对这些患者的有效治疗。
不建议在未检测的情况下(检测具有可行性时)进行经验性治疗，因为在抗生素相关性腹泻的住院患者中大约只有30%患有CDI。
除非怀疑肠梗阻由难辨梭状芽孢杆菌所致，否则仅对腹泻大便进行难辨梭状芽孢杆菌检查(培养或毒素检测)。
在同一次腹泻病患病期间，不建议反复进行难辨梭状芽孢杆菌检查。
在CDI患者发生腹泻期间，建议在私人病房严格执行手部卫生、佩戴手套及穿着隔离服，并实施接触性预防措施。
在病情严重或怀疑并发结肠炎时，等待粪便毒素检测结果期间可对CDI患者开始进行经验性治疗。对于大便毒素检测呈阴性的患者必须实施个体化治疗。
应尽快停用与CDI发生相关的抗生素，因为继续应用会增加CDI复发的风险。尽可能避免使用抑制肠蠕动的药物。
轻中度CDI初次发作时，建议应用甲硝唑(500 mg，po，tid)治疗；而重度CDI初次发作时建议应用万古霉素(125 mg，po，qid)治疗。疗程应为10~14天。CDI并发低血压、肠梗阻或巨结肠者应该应用大剂量万古霉素口服治疗(对肠梗阻的患者，作为灌肠剂经直肠给药)，联合或不联合甲硝唑静脉注射。
对于伴有巨结肠、脓毒血症或肠穿孔的危重患者，应该考虑行保留直肠的结肠次全切除术。血清乳酸和白细胞计数在制定手术决策方面会有所帮助。
以往研究数据显示，在接受过CDI治疗的患者中，高达25%的患者至少有一次复发；年龄在65岁以上、接受甲硝唑治疗的患者复发率相对更高。
CDI首次复发所使用的治疗药物通常与初次发作时相同；但应与初次发作一样，根据病情严重程度分层进行治疗。
甲硝唑不宜用于多次复发的治疗，亦不用于长期治疗。再次或以后的复发应该以万古霉素进行治疗，选用剂量递减疗法或冲击疗法。
参考资料
Cohen S.H., et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect. Control Hosp. Epidemiol. 2010;31:431-55.
Golden博士和Hopkins博士编写的“有效率的医师”(The Effective Physician)栏目是爱思唯尔刊物《内科学新闻》(Internal Medicine News)的常规内容。Golden博士是医学及公共卫生的教授，Hopkins博士是美国小石城阿肯色州大学内科/小儿科联合住院实习期项目的负责人。
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