Treatment of Recurrent Antibiotic-Associated Pseudomembranous Colitis

Eleven patients with relapses of antibiotic-associated pseudomembranous colitis were treated with a tapering dose schedule of vancomycin and cholestipol. All patients responded and have continued to be asymptomatic for follow-up periods of at least 6 wk. This tapering dose of vancomycin in conjunction with cholestipol appears to be warranted in patients with relapses of antibiotic-associated pseudomembranous colitis.     

Bacitracin therapy in antibiotic-associated pseudomembranous colitis

Two patients with antibiotic-associated pseudomembranous colitis and stool positive forClostridium difficile cytotoxin were successfully treated with oral bacitracin. One patient had previously suffered two relapses of pseudomembranous colitis following successful treatment with vancomycin and one patient was allergic to vancomycin. Bacitracin appears to be a reasonable choice to treat patients with antibiotic-associated colitis who are allergic to vancomycin. Further studies comparing vancomycin and bacitracin are needed.     

Yersinia colitis masquerading as pseudomembranous colitis

Summary We describe a 15-month-old male who presented with fever and diarrhea 24 hr after receiving antibiotics for otitis media. A flexible sigmoidoscopy was initially interpreted endoscopically as antibiotic-associated pseudomembranous colitis, and the patient was treated with vancomycin. The diagnosis of antibiotic-associated colitis was excluded in our patient by the negative stool examination forClostridium difficile toxin, the failure to obtain supportive features on rectal biopsy, and the failure to demonstrate sigmoidoscopic improvement with vancomycin therapy. Thirteen days later,Y. enterocolitica was cultured from the initial stool specimens. In this case, the raised central whitish area on an erythematous base was misinterpreted as pseudomembranous colitis.     

Colitis induced by Clostridium difficile

Clostridium difficile has been implicated as the major cause of antibiotic-associated pseudomembranous colitis. The current laboratory diagnostic test of choice is a tissue culture assay that demonstrates the presence of a cytopathic toxin neutralized by antitoxin to Clostridium sordellii. This toxin was found in stools from 42 of 43 patients with antibiotic-associated pseudomembranous colitis and in stools from 12 of 78 patients with antibiotic-associated diarrhea. Specimens from patients with gastrointestinal conditions unrelated to administration of antibiotics and those from healthy controls were uniformly negative. Neutralization of toxin by antitoxin to C. sordellii appears to represent antigenic cross-reactivity, since broth cultures of C. difficile also contain a cytopathic toxin neutralized by this antitoxin. Strains of C. difficile are susceptible to vancomycin, and the initial clinical experience with oral administration of this agent shows promising results.     

Who are Susceptible to Pseudomembranous Colitis Among Patients with Presumed Antibiotic-Associated Diarrhea?

Purpose Pseudomembranous colitis is a severe form of antibiotic-associated diarrhea. However, there have been no reports about the factors that make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. This study was designed to determine the clinical risk factors for pseudomembranous colitis among the patients with presumed antibiotic-associated diarrhea. Methods This was a retrospective study of 150 consecutive patients admitted to our institution between January 2000 and December 2004 with a diagnosis of presumed antibiotic-associated diarrhea. All patients underwent sigmoidoscopy or colonoscopy because of diarrhea after administration of antibiotics. Pseudomembranous colitis was confirmed both endoscopically and histologically. Various clinical parameters were compared between the pseudomembranous colitis group and non-pseudomembranous colitis group. Results The mean age of patients was 61 years, and 60 percent (90/150) was female. Pseudomembranous colitis was diagnosed in 53 percent (80/150). On univariate analysis, older than aged 70 years (P = 0.014), antibiotic therapy for more than 15 days (P < 0.0001), hospital stay for more than 20 days (P < 0.0001), number of antibiotics used more than one (P = 0.01), and surgical procedures (P = 0.029) were significant parameters for pseudomembranous colitis. On multivariate analysis, the important clinical risk factors were advanced age (older than aged 70 years; adjusted odds ratio, 2.7; 95 percent confidence interval, 1.208–6.131; P < 0.016) and long hospital stay (more than 20 days; adjusted odds ratio, 5.1; 95 percent confidence interval, 2.1–12.259; P < 0.0001). When both risk factors were present, the positive predictive value of pseudomembranous colitis was 0.86. Conclusions Advanced age and long hospital stay may make patients with presumed antibiotic-associated diarrhea susceptible to pseudomembranous colitis. Therefore, pseudomembranous colitis should be first suspected in cases with presumed antibiotic-associated diarrhea having such risk factors. Poster presentation at the meeting of the Asian-Pacific Digestive Week 2005, Seoul, Republic of Korea, September 25 to 28, 2005.     

Antibiotic-associated fulminant pseudomembranous colitis without toxic megacolon.

Presented is a middle-aged male who developed a fulminant case of antibiotic-associated pseudomembranous colitis characterized by leukocytosis, hypoalbuminemia, ascites, and anasarca without toxic megacolon. The patient responded slowly to medical therapy consisting of intravenous metronidazole, oral vancomycin, and parenteral nutrition. Subsequently, cholestyramine was administered. A review of the literature concerning similar cases of fulminant pseudomembranous colitis is presented.     

Treatment of Clostridium difficile colitis and diarrhea with vancomycin

Toxigenic Clostridium difficile is the major cause of antibiotic-associated colitis and is susceptible to vancomycin at fecal concentrations achieved with oral therapy. The effect of oral vancomycin was studied in 16 patients with C. difficile-related diarrhea or colitis, 12 of whom had colitis documented by endoscopy, biopsy, and/or barium enema. Four patients had antibiotic-associated diarrhea and possibly antibiotic-associated colitis, because sigmoidoscopy either showed normal results (two patients) or was not performed (two patients). Nineteen episodes of diarrhea were treated with oral vancomycin in two dosage regimens for three to 14 days. Twelve patients received 2 g daily, and four patients initially received 1 g or less per day. Within 48 hours of the start of vancomycin therapy, 14 of 16 patients (87 percent) showed a decrease in temperature, abdominal pain and diarrhea. Diarrhea ceased completely within two days of the start of vancomycin in nine episodes, within three to seven days in six episodes, and within eight to 14 days in the remaining four episodes. Diarrhea recurred in two of these patients (12 percent) when the drug inciting the initial episode of colitis was given again 42 days or more after vancomycin therapy was stopped; both patients responded again to retreatment with vancomycin. Oral vancomycin is an effective treatment of C. difficile-related colitis and diarrhea.     

Therapy of antibiotic-associated pseudomembranous colitis.

Seven patients treated with oral cholestyramine for antibiotic-associated pseudomembranous colitis are reported. Response was variable with only one patient having a totally satisfactory clinical outcome. Five of seven patients had continued systemic signs with fever and leukocytosis throughout the course of cholestyramine. Two observations were relatively consistent. First, six of the seven patient had a decrease in the number of daily stools during therapy. Second, all patients showed persistence of the cytopathic toxin in stools obtained after three to seven days of cholestyramine therapy. Six patients who were subsequently treated with oral vancomycin had a prompt clinical improvement and clearance of the cytopathic toxin in the stool.     

Morphology of experimental antibiotic-associated enterocolitis in the hamster: a model for human pseudomembranous colitis and antibiotic-associated diarrhoea.

The morphology of antibiotic-associated enterocolitis in the hamster is described and compared with human antibiotic-associated pseudomembranous colitis. It is shown to be a caecal disease with proliferative mucosal changes and in this respect unlike the human counterpart. The bacteriology and toxicology, however, are identical. In addition, mucosal changes are described in animals on antibiotics but without established enterocolitis. As a result we suggest that there may be a spectrum of human disease ranging from mild antibiotic-associated diarrhoea to established pseudomembranous colitis. Therefore, despite the morphological variation, the hamster remains a good model for investigating the pathogenesis of pseudomembranous colitis and antibiotic-associated enteropathy in general.     

Antibiotic-associated colitis due to Clostridium difficile: double-blind comparison of vancomycin with bacitracin

A randomized double-blind study was carried out in patients with unresolving antibiotic-associated colitis due to Clostridium difficile, to compare the effect of bacitracin (80,000 U/day) with vancomycin (500 mg/day) on the resolution of symptoms, clearance of organism, and prevention of relapse. Forty-two patients with colitis, 9 of whom had a pseudomembrane, were randomized, 21 patients to each treatment group. The two groups were comparable in age, disease severity, and antibiotic exposure. For a 50% reduction in stool frequency the mean times (+/- SE) were 4.1 +/- 0.4 days for bacitracin and 4.2 +/- 0.4 days for vancomycin. Sixteen patients (76%) had symptom resolution after 7 days of treatment with bacitracin, compared with 18 patients (86%) given vancomycin. Patients who failed to respond were crossed over (blind) to the alternative antibiotic, but tended to be refractory to the alternative medication as well. Vancomycin-treated patients had negative toxin (83% vs. 53%, p = 0.04) and negative stool cultures (81% vs. 52%, p = 0.02) more frequently than did those patients given bacitracin. Similar numbers of patients in each group had symptomatic relapse during 1 mo of follow-up, but most of them relapsed yet again after blinded crossover therapy. Although bacitracin was significantly less effective than vancomycin in clearing C. difficile from the stools, both were of similar value in the control of symptoms in a group of patients with predominantly nonpseudomembranous colitis. In view of its low cost, bacitracin is a reasonable first-line alternative to vancomycin in the treatment of antibiotic-associated colitis.     

Post-antibiotic diarrheas: role of Klebsiella oxytoca]

From May 1989 to January 1991, 20 patients were investigated for antibiotic-associated acute diarrhea. Colonoscopy or rectosigmoidoscopy was performed in each patient. Cultures of colonic mucosal biopsies were carried out using conventional culture grounds (cystine-lactose-electrolyte-deficient). The aim of this study was to investigate the role of a gram negative bacillus: Klebsiella oxytoca. Among the 20 patients with antibiotic-associated acute diarrhea, 11 had bloody and mucus diarrhea and colitis ranging from a right-sided hemorrhagic to diffuse acute ulcerative or erosive colitis, 7 had a grossly normal colonic appearance, while 2 had mucus diarrhea and pseudomembranous colitis. Of colonic biopsies cultures obtained from 36 control patients, 15 had a normal colonic appearance, 15 had ulcerative or crohn's colitis, 6 had well-tolerated amoxicillin therapy. Klebsiella oxytoca was never found in the 36 control patients; Klebsiella oxytoca was noted among 8/11 patients with mucus-discharging and bloody diarrhea. These results suggest that antibiotic-associated, non pseudomembranous colitis is frequently associated with Klebsiella oxytoca infection, which may be the cause of this type of colitis.     

Repeated Clostridium difficile infection after living donor liver transplantation

Liver transplant recipients are considered to be at high risk for Clostridium difficile infection, with an incidence of 2.7–8.0%, which is three times higher than that among other patients. A case of a patient who suffered from pseudomembranous colitis five times after living donor liver transplantation is reported. A 60-year-old woman underwent splenectomy and living donor liver transplantation using the left lobe of her spouse for primary biliary cirrhosis. The patient made a satisfactory recovery, except for splenic vein thrombosis. She was discharged on postoperative day 36; however, she developed pseudomembranous colitis due to Clostridium difficile infection five times within 6 months after transplant and was treated with oral vancomycin each time. At the fifth recurrence of pseudomembranous colitis, the patient received vancomycin taper treatment, dietary counseling, and repeat instructions regarding hand hygiene and house cleaning. The patient recovered and is currently well without recurrence of Clostridium difficile infection 36 months after living donor liver transplantation.     

Rifampicin-associated pseudomembranous colitis

We report a case of pseudomembranous colitis that developed in a patient with liver cirrhosis during anti-tuberculosis therapy with rifampicin and isoniazid. The association between rifampicin and pseudomembranous colitis has been controversial; this report, however, supports the association. Colonoscopy performed 3 days after the onset of the pseudomembranous colitis revealed only reddish patches and a few aphthoid lesions, but 4 days later pseudomembranes were apparent. The pseudomembranous colitis was successfully controlled by discontinuation of the anti-tuberculosis agents, along with the administration of lactic acid bacteria, without vancomycin or metronidazole. Possible predisposing factors for the development of pseudomembranous colitis in this patient are also discussed. Received: February 8, 1999 / Accepted: August 27, 1999     

Clostridium difficile infection: risk factors, medical and surgical management

BACKGROUND: Clostridium difficile has become recognized as a cause of nosocomial infection which may progress to a fulminant disease. METHODS: Literature review using electronic literature research back to 1966 utilizing Medline and Current Contents. All publications on antibiotic-associated diarrhea, antibiotic-associated colitis, and pseudomembranous colitis as well as C. difficile infection were included. We addressed established and potential risk factors for C. difficile disease such as an impaired immune system and cost benefits of different diagnostic tests. An algorithm is outlined for diagnosis and both medical and surgical management of mild, moderate and severe C. difficile disease. RESULTS: Diagnosis of C. difficile infection should be suspected in patients with diarrhea, who have received antibiotics within 2 months or whose symptoms started after hospitalization. A stool specimen should be tested for the presence of leukocytes and C. difficile toxins. If this is negative and symptoms persist, stool should be tested with 'rapid' enzyme immunoabsorbent and stool cytotoxin assays, which are the most cost-effective tests. Endoscopy and other imaging studies are reserved for severe and rapidly progressive courses. Oral metronidazole or vancomycin are the antibiotics of choice. Surgery is rarely required for selected patients refractory to medical treatment. The threshold for surgery in severe cases with risk factors including an impaired immune system should be low. CONCLUSION: C. difficile infection has been recognized with increased frequency as a nosocomial infection. Early diagnosis with immunoassays of the stool and prompt medical therapy have a high cure rate. Metronidazole has supplanted oral vancomycin as the drug of first choice for treating C. difficile infections.     

重视腰椎外伤手术患者的胃肠道症状

腰椎外伤和腰椎手术患者由于腹膜后血肿和手术刺激腹腔神经丛导致不同程度的胃肠功能障碍.严重者出现肠麻痹和腹膜炎,患者出现严重腹胀、腹痛、不能进食.在此基础上术后应用抗生素时易出现抗生素相关性腹泻,严重者出现重度伪膜性肠炎.由于骨科医师对伪膜性肠炎不认识,消化科医师又对伪膜性肠炎可出现腹腔内高压甚至腹腔间隔室综合征不认识或重视观察处理不够,错过了在腹腔内高压时段抢救的最佳时机,导致患者死亡,因此对腰椎外伤和腰椎手术患者要高度重视早期胃肠道症状,及时发现抗生素相关性腹泻,尤其重度伪膜性肠炎的出现.重视腹腔内高压的有效处理,防止腹腔间隔室综合征的出现,降低死亡率.     

Absence of Diarrhea in Toxic Megacolon Complicating Clostridium difficile Pseudomembranous Colitis

We describe a patient with Clostridium difficile-associated pseudomembranous colitis who presented with toxic megacolon without diarrhea. The discussion includes a brief review of the literature, and suggests an important role for endoscopy in the diagnosis of pseudomembranous colitis and, possibly, as part of the therapy for toxic megacolon associated with Clostridium difficile colitis. The unusual combination of toxic megacolon without antecedent diarrhea should be recognized as a possible manifestation of antibiotic-associated pseudomembranous colitis, especially in the setting of simultaneous antimicrobial and opiate administration. Early diagnosis and disease-specific intervention can be lifesaving.     

Tube feeding, the microbiota, and Clostridium diff icile infection

Clostridium difficile (C. difficile) is now the leading cause of nosocomial diarrhea in the USA, accounting for 30% of patients with antibiotic-associated diarrhea, 70% of those with antibiotic-associated colitis, and most cases of pseudomembranous colitis. The organism has evolved over the last 8 years to become more virulent and resistant to antimicrobials (NAP1/027 strain) causing a more severe form of the disease that has increased mortality and healthcare costs. While it is generally accepted that the ...     

伪膜性肠炎的内镜与临床特征研究

目的 通过对抗生素所致伪膜性肠炎(pseudrmembranous colitis,PMC)的内镜下诊断分析,总结其内镜下特征,提高诊治水平.方法 对我院近3年来内科诊治的17例PMC进行回顾性分析.结果 PMC多发于合并有长期慢性疾病、年龄大、体质差及抗生素应用不规范的老年患者,17例病人中,14例系老年重症患者.全部患者均在使用广谱抗生素过程出现腹泻、腹痛、血便等症状.均接受结肠镜检查,提示为PMC.结论 结肠镜检杳是诊断PMC快速而可靠的方法.重视对内科老年人及重症病患者,对长期大量使用抗生素的老年患者出现腹痛、腹泻时,结合结肠镜的特征表现首先应考虑有无PMC,及早停用抗生素,使用足量和足疗程的甲硝唑和万古霉素和相应的微生态制剂是治疗PMC有效方法.     

Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens

PURPOSE: High-dose (500 mg orally four times daily) vancomycin is considered by many investigators to be the most effective treatment for antibiotic-associated Clostridium difficile colitis. However, a lower dosage of 125 or 150 mg given three or four times a day has become popular, has been shown to be effective, and is less expensive than the high-dose regimen. We therefore decided to compare two vancomycin dosage regimens in a randomized trial. PATIENTS AND METHODS: The study involved 46 hospitalized patients with serious underlying diseases complicated by C. difficile diarrhea or colitis. Patients were assigned (according to a table of random numbers) to treatment with either 125 or 500 mg of vancomycin orally four times daily for an average of 10 days. RESULTS: No significant differences in measurable responses to the two regimens were noted. There were no treatment failures. The mean duration of diarrhea after initiation of therapy was about four days, and almost all patients had no diarrhea after one week. The organism continued to be demonstrated in the stools of about 50 percent of patients for the first few weeks after completion of therapy, and nine (20 percent) patients developed a recurrence of their diarrheal illness. Vancomycin was well tolerated by all patients. CONCLUSION: Since the dose of 125 mg appeared to be as effective as the 500-mg dose, which is more expensive, the 125-mg dose is preferred when vancomycin is used in treatment of this disease, unless the patient is critically ill.     

Recurrent pseudomembranous colitis as a cause of recurrent severe sepsis

Clostridium difficile (C. difficile) colitis accounts for nearly 15-20 % of antibiotic-associated diarrhea. Manifestations include asymptomatic carriage, self-limited diarrhea, and pseudomembranous colitis, which is sometimes life-threatening. Despite effective therapy with metronidazole and vancomycin relapse rates are 15-33 %. Although colitis is seen in critically ill patients treated with combinations of broad-spectrum antibiotics, reports describing severe sepsis as a result of C. difficile infection are limited. We describe the case of recurrent severe sepsis due to recurrent local intestinal C. difficile infection as the only identifiable etiology. The mechanism of severe sepsis may be a derangement of the gastrointestinal barrier function. This could result in absorption of microbes or endotoxin or activation of inflammatory cascades in the submucosa of the intestine or liver. In general, for successful treatment of C. difficile infections other than anticlostridial antibiotics should be discontinued. However, in the present case bacterial translocation from the intestine is an attractive explanation for severe sepsis and therefore additional antibiotics had been administered.