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艰难梭菌所致结肠炎的最新进展,第2部分。

Update on Clostridium difficile-induced colitis, Part 2.

作者信息

Reinke C M, Messick C R

机构信息

Department of Clinical Pharmacy Practice, School of Pharmacy, Auburn University, AL 36849-5502.

出版信息

Am J Hosp Pharm. 1994 Aug 1;51(15):1892-901; quiz 1958-9.

PMID:7942924
Abstract

Clostridium difficile is a nosocomial pathogen able to survive unfavorable environments by sporulation; when conditions advantageous for rapid growth appear, the vegetative form is regenerated. Lack of conscientious hand washing and failure of health care providers to use disposable gloves facilitate transmission within institutions. Exposure to certain antimicrobials expedites C. difficile overgrowth within the colon by altering the composition of the normal gut microflora. Antineoplastic agents may also precipitate CDIC. The characteristics of the colonizing strain, the properties of the inciting drug, and individual host factors collectively seem to govern the expression of the disorder. Clinical presentations range from self-limiting diarrhea to severe diarrhea accompanied by abdominal pain, fever, and leukocytosis to potentially life-threatening PMC. A preponderance of data supports the interpretation that oral metronidazole and oral vancomycin are therapeutically equivalent for the treatment of all but the most severe cases of CDIC. Whether the two drugs are equivalent in severe CDIC is controversial and will probably remain so in the absence of a well-designed trial to expand on the findings of the study by Teasley et al. Because of the cost difference and therapeutic equivalence, oral metronidazole should be the preferred routine treatment for CDIC; oral vancomycin should be reserved for severe cases and cases that fail to respond to at least six days of oral metronidazole therapy. Another important argument, albeit a hypothetical one, for limiting institutional use of oral vancomycin is to minimize selective environmental pressure for the emergence and dissemination of vancomycin-resistant enterococci. An epidemic outbreak of CDIC caused by clindamycin-resistant C. difficile in an institution where clindamycin use was extremely high illustrates the possible consequences of such selective pressure. Oral metronidazole 250 mg four times daily will usually provide a satisfactory response, but clinicians may wish to consider increasing the total daily dose for some patients who have symptoms like fever and leukocytosis. For oral vancomycin, 125 mg four times daily is sufficient in virtually all circumstances. Ten days of therapy is usually adequate for either drug. CDIC in a patient unable to take medications orally presents a bit of a therapeutic dilemma. Two approaches that appear effective are rectal administration of vancomycin and intravenous administration of metronidazole, although intravenous metronidazole can fail to work, possibly because the colonic concentrations achieved are inadequate. Clinicians may wish to consider a total daily dose of intravenous metronidazole that is at the upper end of the adult dosage range, if this is feasible.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

艰难梭菌是一种医院病原体,能够通过形成芽孢在不利环境中存活;当有利于快速生长的条件出现时,又会重新生成营养体形式。医护人员缺乏认真洗手以及未使用一次性手套,会促使该病菌在医疗机构内传播。接触某些抗菌药物会改变正常肠道微生物群的组成,从而加速艰难梭菌在结肠内过度生长。抗肿瘤药物也可能引发艰难梭菌相关性腹泻(CDIC)。定殖菌株的特性、诱发药物的性质以及个体宿主因素共同决定了该病症的表现形式。临床表现范围从自限性腹泻到伴有腹痛、发热和白细胞增多的严重腹泻,甚至发展为可能危及生命的伪膜性结肠炎(PMC)。大量数据支持这样的解读:对于除最严重的CDIC病例外,口服甲硝唑和口服万古霉素在治疗上等效。在严重CDIC中这两种药物是否等效存在争议,并且在没有精心设计的试验以扩展Teasley等人的研究结果的情况下,可能仍会存在争议。由于成本差异和治疗等效性,口服甲硝唑应是CDIC的首选常规治疗药物;口服万古霉素应保留用于严重病例以及对至少六天的口服甲硝唑治疗无反应的病例。另一个限制医疗机构口服万古霉素使用的重要理由,尽管是假设性的,是为了尽量减少对万古霉素耐药肠球菌出现和传播的选择性环境压力。在一个克林霉素使用量极高的机构中,由耐克林霉素的艰难梭菌引起的CDIC疫情爆发,说明了这种选择性压力可能带来的后果。口服甲硝唑每日250毫克,分四次服用,通常会有满意的疗效,但对于有发热和白细胞增多等症状的一些患者,临床医生可能希望考虑增加每日总剂量。对于口服万古霉素,几乎在所有情况下每日125毫克,分四次服用就足够了。两种药物通常治疗十天就足够了。对于无法口服药物的患者,CDIC会带来一些治疗难题。两种似乎有效的方法是万古霉素直肠给药和甲硝唑静脉给药,尽管静脉注射甲硝唑可能无效,可能是因为达到的结肠浓度不足。如果可行的话,临床医生可能希望考虑使用成人剂量范围上限的甲硝唑每日总静脉剂量。(摘要截选至400字)

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引用本文的文献

1
Metronidazole. A therapeutic review and update.甲硝唑:治疗综述与更新
Drugs. 1997 Nov;54(5):679-708. doi: 10.2165/00003495-199754050-00003.
2
Drug-induced Clostridium difficile-associated disease.药物性艰难梭菌相关性疾病
Drug Saf. 1997 Jul;17(1):37-46. doi: 10.2165/00002018-199717010-00003.