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.     

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.     

Approach to Patients with Multiple Relapses of Antihiotic-Associated Pseudomembranous Colitis

Twenty-two patients with multiple relapses of antibiotic-associated pseudomembranous colitis underwent a tapering dose of oral vancomycin for 21 days and a pulse dose of vancomycin for 21 days. In follow-up ranging from 2-12 months with a mean of 6 months, all patients have been without recurrence of the antibiotic-associated pseudomembranous colitis.     

Recurrent Clostridium difficile-associated colitis responding to cholestyramine

We describe a patient with relapses of Clostridium difficile cytotoxin-positive pseudomembranous colitis (PMC) after treatment with vancomycin, a course of metronidazole and a trial of bacitracin. She remains free of disease after a prolonged course of cholestyramine. We suggest there may be a role for anion-exchange resins in patients with PMC relapsing after vancomycin therapy.     

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.     

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.     

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.     

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.     

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.     

Oral bacitracin vs vancomycin therapy for Clostridium difficile-induced diarrhea. A randomized double-blind trial

The effectiveness of a ten-day course of either oral bacitracin or oral vancomycin hydrochloride for treatment of Clostridium difficile-induced antibiotic-associated diarrhea was compared in a randomized double-blind study. Bacitracin was as effective as vancomycin in resolving diarrhea; most patients responded within five days of therapy with either drug. Three patients receiving bacitracin worsened during therapy; two of these were considered treatment failures. Neither C difficile nor its toxin was detected in stool samples collected on the final day of therapy in 71% of patients (10/14) receiving vancomycin and in 30% (3/10) receiving bacitracin. Five patients receiving bacitracin and three receiving vancomycin had at least one recurrence. Low but nontoxic concentrations of bacitracin were detected in serum samples collected from 11 patients. Oral bacitracin at this dosage level was as effective as vancomycin in resolving the symptoms of C difficile-induced antibiotic-associated diarrhea in most patients but was less effective in eradicating C difficile and its toxin from patients' stools.     

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.     

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.     

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.     

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.     

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     

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.     

PSEUDOMEMBRANOUS COLITIS: PRESENCE OF CLOSTRIDIAL TOXIN

A toxin was found in the fæces of nine out of nine patients with pseudomembranous colitis and two out of two with antibiotic-associated non-specific colitis. The toxin was neutralised by Clostridium sordellii antitoxin but not by a commercial mixture of C. welchii, œdematiens, and septicum antitoxins. The in-vitro and in-vivo properties of pseudomembranous-colitis toxin closely resemble those of the toxin of C. sordellii.     

Prevention of further recurrences ofClostridium difficile colitis withSaccharomyces boulardii

Summary A patient with six documented episodes of recurrentClostridium difficile colitis over an eight-month period is described. Relapses of colitis occurred despite treatment with vancomycin, metronidazole, bacitracin, and cholestyramine. Each recurrence appeared to begin successively closer to the end of the previous course of treatment. Four episodes were sufficiently severe to require hospitalization for rehydration.Saccharomyces boulardii, a nonpathogenic yeast, was begun prior to discontinuing vancomycin therapy for the last recurrence and was continued for three months. Serial stool cultures and assays forC. difficile showed persistence of the organism but rapid reduction of high titers of cytotoxin. No further recurrences of diarrhea or colitis were encountered while the patient was takingSaccharomyces boulardii and for 18 months of follow-up after the yeast was discontinued.     

The potential for emerging therapeutic options for Clostridium difficile infection

Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review.