Case Discussion Case Presentation: A 75-year-old woman was consulted for a 1-week history of diarrhea and fever. She had an ischemic stroke about 5 years ago and then became bedridden. One month earlier she had undergone a plastic surgery for bedsore. During hospitalization, she received intravenous antibiotics. Owing to some purulent discharge from the wound, she was sent home from the hospital with a prescription for oral clindamycin, 300mg four times a day, which she had taken for 2 weeks. However, fever developed since one week ago and an accompanied diarrhea for 3 days. She was admitted to the plastic ward for the second time. After taken the blood culture, treatment was started with intravenous cefamezin. However, fever and diarrhea seemed to be worse. A gastroenterologist was then consulted. Physically, she was acute ill-looking. The blood pressure was 160/90 mmHg, the pulse was 90/min, and the temperature was 39。C. A 4cm surgical wound was found at sacral area with scanty discharge. Her abdomen showed tenderness over lower abdomen without rebounding pain. The other physical examinations were unremarkable. Laboratory tests were performed. 1. Hematologic Laboratory Values:   RBC Hb Hct MCV Platelet WBC MCHC   M/μL g/dL % fl k/μL k/μ g/dL On Admission 4.78 14.2 42.6 90.1 320 17.8 33   Seg Eos Baso Mono Lym       % % % % %       89.5 3 0.1 1.9 5.5     2. Stool Examination: Occult blood: 3+ Stool WBC: Numerous / HPF Stool culture: Negative Course and Treatment: A colonoscopy was performed after consultation and it showed multiple raised, yellowish, and plaque-like pseudomembranes over the entire colon (Figure 1 .). Clostridium difficile-toxin was also recovered from the stool. Oral metronidazole 250mg four times a day was prescribed under the diagnosis of pseudomembranous colitis. Fever and diarrhea dramatically subsided after a 10-day treatment. Case Analysis: Pseudomembranous colitis is caused by Clostridium difficile and develops in patients whose gastrointestinal microbio has been changed by the use of antibiotics. In healthy individuals, these normal microbio effectively inhibits C. difficile by making host receptors unavailable, competing for available nutrients, or producing bacteriotoxins. The antibiotic clindamycin is the drug most frequently associated with C. difficile infections, followed by ampicillin and cephalosporin. At least two toxins of C. difficile are recognized: toxin A, or enterotoxin, and toxin B, or cytotoxin. Diagnosis generally requires isolation of the organism from stool samples although C. difficile is difficult to culture. Immunoassays for the toxins should be made to confirm a positive toxin titer. Endoscopic observation of pseudomembranes in the colon is the means for confirmative diagnosis. Diarrhea caused by pseudomembranous colitis may be a self limited condition that resolves with fluid, electrolyte support and cessation of antibiotics treatment. Oral metronidazole is the drug of choice as it is less expensive that oral vancomycin. It has antianaerobic properties and avoids development of fecal enterococcal resistance to vancomycin. Proper diagnosis is important to prevent the development of pseudomembranous colitis and C. difficile should be suspected in those who are immunosuppressed or other risk-associated debilitated population groups with serious diarrhea. 繼續教育考題 1. (A) Clostridium difficile is : A Gram-positive, obligate anaerobe. B Gram-positive, aerobe. C Gram-negative, obligate anaerobe. D Gram-negative, aerobe. 2. (E) Clostridium difficile associated colitis tends to affect : A Debilitated patients. B Elderly patients. C Persons with recent gastrointestinal procedures or surgery. D Those who are immunosurpressed because of cancer treatment or AIDS. E All of above. 3. (C) Most frequent drug associated with pseudomembranous colitis is: A Ciprofloxacin. B Clarithromycin. C Clindamycin. D Chloramphenicol. E Gentamycin. 4. (A) What is the most frequent symptom of pseudomembranous colitis: A Watery diarrhea. B Bloody diarrhea. C Fever. D Abdominal pain. E  Rebound tenderness. 5. (D) The most rapid way for confirmative diagnosis of pseudomembranous colitis is: A Latex agglutination assays for toxins. B Isolation of the organism from stool samples. C Immunoassays for the toxins. D Endoscopic observation of pseudomembranes in the colon. E Tissue cytotoxic assays. 6. (D) What is not a treatment modality of pseudomembranous colitis: A Oral metronidazole. B Oral vancomycin. C Oral bacitracin. D Antiperistalsis agent. E Cholestyramine plus Lactobacillus. 7. (B) What is the characteristically endoscopic appearance of pseudomembranous colitis: A Submucosal ecchymosis and hemorrhage. B Mucosal plaque-like lesions. C Longitudinal ulcerations. D Erythematous and edematous mucosa. E Fistula formation. 8. (A) In what condition the rate of C. difficile isolation is the highest A Antibiotic-associated colitis with positive toxin assay. B Hospitalized patients. C Healthy neonates. D Antibiotic exposure without diarrhea. E Antibiotic-associated diarrhea. 9. (E) What is the correct statement concerning the characters of antibiotic-associated colitis due to C. difficile in comparison with enigmatic cases: A Usually not dose related. B Response to drug withdrawal. C Complication can be severe. D Tends to be epidemic or endemic in hospitals and nursing homes. E All of above. 10. (E) What testing modality has the lowest diagnostic rate for pseudomembranous colitis:  A Stool culture. B Stool cytotoxin assay. C Stool enzyme immunoassay. D Flexible proctosigmoidoscopy. E Barium enema examination. 答案解說 (A) Clostridium difficile is a gram-positive, obligate anaerobe that received its name because of the difficulty of devising methods for its isolation. (E) Major risk factors for pseudomembranous colitis include old age, immunosuppression, hospitalization, and procedures or medications that alter intestinal motility or flora (C) The most frequent causative antibiotics of pseudomembranous colitis include clindamycin, ampicillin, and cephalosporin (A) Clinical features of pseudomembranous colitis are listed below: Feature Frequency (%) Watery diarrhea 90-95 Bloody diarrhea 5-10 Fever 80 Abdominal pain 80-90 Rebound tenderness 10-20 (D ) In patients with pseudomembranous colitis, endoscopy provides the most rapid and definitive diagnosis. (D) Specific therapy of pseudomembranous colitis is based on 3 approaches: Utilizing antibiotics effective against C. difficile (metronidazole, vancomycin, or bacitracin), Eliminating the toxin from the colonic lumen with binding resins (cholestyramine, or colestipol) Re-establishing the normal colonic flora (oral Lactobacillus or Saccharomyces boulardii). * The use of antiperistaltic drugs is thought to increase the risk of toxic megacolon. (B ) Typically, endoscopic findings of pseudomembranous colitis are small, yellowish, discrete, and raised plaques. (A) Isolation rates of C. difficile in stool specimens are listed below: Category of patients Culture positive (%) Colitis with positive toxin assay 90-100 Hospitalized patients 10-20 Healthy neonates 30-60 Antibiotic exposure without diarrhea 10-50 Antibiotic-associated diarrhea 10-30 (E) In nearly all cases of pseudomembranous colitis, C. difficile is the pathogen. However, most patients with antibiotic-associated diarrhea do not have C. difficile toxin. The issue confronting the clinician is the clinical features or clues that permit bedside determination of the probability that a patient has C. difficile-associated disease in the setting of antibiotic-associated diarrhea. The comparison of antibiotic-associated diarrhea/colitis is listed below: Variable C. difficile Cause unknown Relationship of illness to dose Usually not dose related Dose related Response to drug withdrawal Symptoms often persist Symptoms usually resolve Complications Can be severe Rarely serious Epidemiology Epidemic or endemic in hospitals and nursing homes Sporadic (E)Radiographic examination of the pseudomembranous colitis may be suggestive but is rarely diagnostic.