Clostridium Difficile Infection

Key Features

Essentials of Diagnosis

• Infection leads to a spectrum of clinical disease, from asymptomatic colonization to severe pseudomembranous colitis with fever, severe abdominal pain, and bloody diarrhea

• Risk factors for C difficile disease

  • Previous antibiotic use

  • Presence of various chronic diseases, such as immunodeficiency, cystic fibrosis, Hirschsprung disease, inflammatory bowel disease

  • Oncologic treatments

  • Solid-organ transplantation

  • Hospitalization

• Community-acquired C difficile disease in healthy persons is increasing in incidence

General Considerations

• C difficile is a spore-forming gram-positive bacillus

• Causes human disease via the secretion of enterotoxins that cause necrotizing inflammation of the colon

• Interestingly, asymptomatic C difficile colonization of the human gastrointestinal (GI) tract occurs commonly in infants and can occur in older children and adults as well

Clinical Findings

• Characteristics of pseudomembranous colitis

  • Fever

  • Abdominal distention

  • Tenesmus

  • Diarrhea

  • Generalized abdominal tenderness

• Chronic presentations with low-grade fever, diarrhea, and abdominal pain have been described

Diagnosis

Laboratory Findings

• Diarrheal stools contain sheets of neutrophils and sometimes gross blood

• Use of real-time polymerase chain reaction (PCR) for toxin identification has been replacing more traditional enzyme immunoassay (EIA) methods of stool toxin detection because of improved sensitivity

• C difficile can be cultured in specialized laboratories

Imaging

• Plain abdominal radiographs show a thickened colon wall and ileus

• On endoscopy, the colon appears to be covered by small, raised white plaques (pseudomembranes) with areas of apparently normal bowel in between

Diagnostic Procedures

• Biopsy specimens show "exploding crypts or volcano lesion"—an eruption of white cells that appears to be shooting out of affected crypts

• Stool cultures often show overgrowth of Staphylococcus aureus, which is probably an opportunistic organism growing in the necrotic tissue

• Interpretation of C difficile diagnostic testing in infants remains controversial because asymptomatic colonization is well recognized in the first year of life

Treatment

• Standard treatment of pseudomembranous colitis

  • Discontinue antibiotics

  • Start oral metronidazole (30 mg/kg/d) or vancomycin (30–50 mg/ kg/d)

    • Metronidazole can be given intravenously in patients with vomiting or ileus

    • Vancomycin is many times more expensive than metronidazole and no more efficacious

• Rifaximin and nitazoxanide

  • Alternative options

  • Both show similar response rates as oral vancomycin

• Same antibiotic regimen is usually effective in managing relapses

• Fecal bacteriotherapy, known popularly as fecal transplantation, is now a widely accepted and nearly 100% effective treatment for the treatment of recurrent C difficile infection in adults but experience remains limited in children

• Adjunctive strategies have been used for refractory disease

  • Saccharomyces boulardii probiotic therapy

  • Cholestyramine as a toxin-binder

  • Pulsed courses of antibiotics

Outcome

Prognosis

• Incidence, morbidity, and mortality of C difficile has increased in Europe, Canada, and ...