Andréjak M, Schmit J L, Tondriaux A
Service de Pharmacologie Clinique, Centre Hospitalier Régional et Universitaire, Amiens, France.
Drug Saf. 1991 Sep-Oct;6(5):339-49. doi: 10.2165/00002018-199106050-00004.
Antibiotic-associated pseudomembranous colitis is an uncommon but potentially serious adverse reaction, resulting in acute diarrhoea and characterised by colonic pseudomembranes. A direct relationship between the disease, recent antibiotic therapy and proliferation of Clostridium difficile in the colonic lumen was established in the late 1970s. It is thought that antibiotic therapy may alter the enteric flora, enabling C. difficile to proliferate and produce toxins with cytopathic (toxin B or cytotoxin) and hypersecretory (toxin A or enterotoxin) effects on the mucosa. Apart from clindamycin, the first antibiotic recognised to be clearly associated with pseudomembranous colitis, the antimicrobial agents most commonly responsible are cephalosporins and ampicillin (or amoxicillin). However, virtually all antibiotics except parenterally administered aminoglycosides can cause the disease. Vancomycin and metronidazole, 2 drugs used to treat antibiotic-associated pseudomembranous colitis, have also been reported to be responsible for the complication when used parenterally. Pseudomembranous colitis may develop after perioperative prophylactic antibiotic therapy with cephalosporins. Antibiotic-associated pseudomembranous colitis is most frequent in elderly and debilitated patients and in intensive care units. Nosocomial acquisition of C. difficile has been documented. Therefore it has been recommended that enteric isolation precautions should be taken with patients with this disease. The clinical symptoms include watery diarrhoea, abdominal cramping, and frequently fever, leucocytosis and hypoalbuminaemia. Toxic megacolon and acute peritonitis secondary to perforation of the colon are the most serious complications. The pseudomembranes are usually seen during endoscopic procedures, sigmoidoscopy or, if possible, colonoscopy; the most useful microbiological tests for confirmation of the diagnosis include cycloserine cefoxitin fructose agar (CCFA) stool cultures and stool toxin assays on tissues or by immunological techniques. However, cultures and toxin tests may be positive in patients without pseudomembranous colitis or C. difficile-associated diarrhoea. Mild cases may respond to discontinuation of the drug responsible, but therapy with an anticlostridial antibiotic is often necessary: a 10-day course of oral vancomycin, metronidazole or bacitracin should be given. Relapses are seen in 5 to 50% of patients treated. Antibiotic treatment should avoid sporulation leading to other relapses. 'Biotherapy' (lactobacilli, Saccharomyces) has also been proposed.
抗生素相关性假膜性结肠炎是一种不常见但可能严重的不良反应，表现为急性腹泻并伴有结肠假膜。20世纪70年代末确立了该病、近期抗生素治疗与结肠腔内艰难梭菌增殖之间的直接关系。据认为，抗生素治疗可能改变肠道菌群，使艰难梭菌得以增殖并产生对黏膜具有细胞病变作用（毒素B或细胞毒素）和分泌亢进作用（毒素A或肠毒素）的毒素。除了最早被确认与假膜性结肠炎明确相关的克林霉素外，最常导致该病的抗菌药物是头孢菌素和氨苄西林（或阿莫西林）。然而，实际上除胃肠外给药的氨基糖苷类抗生素外，所有抗生素都可引起该病。用于治疗抗生素相关性假膜性结肠炎的两种药物万古霉素和甲硝唑，胃肠外给药时也有导致该并发症的报道。头孢菌素围手术期预防性抗生素治疗后可能发生假膜性结肠炎。抗生素相关性假膜性结肠炎在老年和体弱患者以及重症监护病房最为常见。已记录到医院获得性艰难梭菌感染。因此，建议对该病患者采取肠道隔离预防措施。临床症状包括水样腹泻、腹部绞痛，常伴有发热、白细胞增多和低白蛋白血症。最严重的并发症是中毒性巨结肠和继发于结肠穿孔的急性腹膜炎。假膜通常在内镜检查、乙状结肠镜检查或（如有可能）结肠镜检查时可见；用于确诊的最有用的微生物学检测包括环丝氨酸头孢西丁果糖琼脂（CCFA）粪便培养以及对组织进行粪便毒素检测或采用免疫技术检测。然而，在没有假膜性结肠炎或艰难梭菌相关性腹泻的患者中，培养和毒素检测也可能呈阳性。轻症病例停用相关药物可能有效，但通常需要使用抗梭菌抗生素治疗：应给予口服万古霉素、甲硝唑或杆菌肽10天疗程。5%至50%接受治疗的患者会出现复发。抗生素治疗应避免导致芽孢形成从而引发其他复发情况。也有人提出了“生物疗法”（乳酸杆菌、酿酒酵母）。
