C. diff Pseudomembranous Colitis (Diarrhea, Campylobacter, Shigella, EPEC)

Questions:

• The most common cause of bacterial diarrhea in children is...Answer

Pseudomembranous colitis

• is a potentially severe diarrheal disease that occurs following exposure to antibiotic therapy and subsequent colonic overgrowth of Clostridium difficile, a gram-positive obligate anaerobic bacillus.
• The organism produces five toxins, the most clinically important of which are toxins A and B.
• These toxins bind to receptors on the colonic mucosa and stimulate an inflammatory reaction.
• Toxin A is considered the predominant virulence factor.
• Toxin A is an enterotoxin that causes fluid secretion, increased vascular permeability, and inflammation of intestinal tissue
• Toxin B, a cytotoxin, injures the colonic tissue.

Causes

• Pseudomembranous colitis can develop after the administration of any antibiotic, even agents that are used to treat this disorder.
• Amoxicillin, because of its frequent use in children, is responsible for most cases in the pediatric population.
• Cephalosporins and clindamycin also are associated commonly with its development.
• Several other factors, including gastric acidity, intestinal mucus production, intestinal peristalsis, and the immune response to C difficile infection influence the likelihood of an individual developing pseudomembranous colitis.
• Many neonates and infants (up to 70%) have C difficile isolated from their stools, yet remain asymptomatic carriers.
• It is believed that young infants (younger than 6 months)
  • do not have epithelial cell receptors for toxin adherence
  • develop immunity due to placental maternal antibodies
  • or are protected by maternal colostrum

Spectrum of disease

• variable, ranging from acute, self-limited diarrhea to toxic megacolon.
• The diarrhea typically begins within 10 days of antibiotic administration, although some cases begin as late as 6 weeks later. 
  • Approximately 10% of children who are infected with C difficile will develop pseudomembranous colitis
  • sudden onset of severe diarrhea and crampy abdominal pain.
  • Symptoms often begin within 1 week of the administration of an antibiotic.
  • Tenesmus, vomiting, and high fever complicate the clinical course.
  • Abdominal distension and tenderness are found upon physical examination.
  • Lower gastrointestinal bleeding is often associated with pseudomembranous colitis, as are electrolyte imbalances, leukocytosis, metabolic acidosis, and hypoproteinemia.
• Colonoscopy reveals small plaques of yellow-white exudates (pseudomembranes), petechiae, and friability.
• Toxic megacolon may occur:
  • colonic dilation
  • localized peritonitis, septicemia
  • renal failure
• Other clinical manifestations of C difficile-associated infection include:
  • acute self-limited diarrhea
  • failure to thrive due to chronic infection without colitis,
  • acute flare of inflammatory bowel disease without prior use of antibiotic therapy. 

Management

• Many cases of C difficile infection resolve simply by discontinuing the antibiotic.
• Antiperistaltic medications and corticosteroids may prolong the diarrhea.
• Metronidazole is the treatment of choice for C difficile infection. It is curative in greater than 95% of cases and is the least expensive therapy.
• Vancomycin, which may be more efficacious than metronidazole, is more expensive and, therefore, is considered second-line therapy.
• Oral bacitracin, cholestyramine, and rifampin are alternate therapeutic agents, but they are less effective than metronidazole.
• Relapses occur in up to 15% of cases, even after appropriate antibiotic therapy. Symptoms recur 1 to 4 weeks after discontinuation of therapy.
• A second course of antibiotic therapy is usually effective.
• Third relapses require the use of an alternative antibiotic, a prolonged duration of treatment, or use of combination therapy.
• Recent experience with probiotic therapy involving Saccharomyces boulardii and Lactobacillus GG has been encouraging.
• Whole bowel irrigation with polyethylene glycol solution also has been used successfully in the treatment of chronic intractable C difficile infection.

DDx

• Campylobacter jejuni
• Enteropathogenic Escherichia coli (EPEC)
• The most common cause of bacterial diarrhea in children is Salmonella
• Shigella sp

References:
Bartlett JG. Clostridium difficile: history of its role as an enteric
pathogen and the current state of knowledge about the organism. Clin
Infect Dis. 1994;18(suppl 4):S265-S272
Gorbach SL, Chang TW, Goldin B. Successful treatment of relapsing
Clostridium difficile colitis with Lactobacillus GG. Lancet.
1987;2:1519
Knoop F, Owens M, Crocker IC. Clostridium difficile: clinical disease
and diagnosis. Clin Microbiol Rev. 1993;6:251-265
McFarland LV, Surawicz CM, Greenberg RN, et al. A randomized
placebo-controlled trial of Saccharomyces boulardii in combination
with standard antibiotics for Clostridium difficile disease. JAMA.
1994;271:1913-1918