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  • Alteration of endogenous colonic flora → ingestion of Clostridium difficile spores → colonization → toxin release → necrosis & inflammation
  • Definitions of C. difficile (C. diff) infection: presence of diarrhea (3 or more unformed stools in ≤24h) & presence of toxigenic C. diff or its toxins or pseudomembranous colitis by colonoscopic or histopathological findings (Infect Control Hosp Epidemiol 2010;31:431)
    • Risk factors: advanced age, duration of hospitalization, antimicrobial use (esp. clindamycin, cephalosporins, fluoroquinolones), chemotherapy, immunosuppression, GI surgery or manipulation, acid-suppressing medications (H2 blockers & PPIs), feeding tubes (especially postpyloric) (Infect Control Hosp Epidemiol 2010;31:431; Clin Infect Dis 2008;46:S19)

(Infect Control Hosp Epidemiol 2010;31:431; Clin Infect Dis 2008;46:S12)

  • Suspect C. diff in patients with diarrhea & any of the above risk factors, although cases have been reported without any known risk factors.
    • Marked leukocytosis (anywhere from 10K to 100K) may be seen with C. diff infection, which likely reflects the severity of colonic inflammation (Infect Control Hosp Epidemiol 2010;31:431); however, leukocytosis not always present & normal WBC count should not rule out C. diff
  • Most diagnostic testing has been developed to detect toxin B &/or A; testing only performed on unformed stools
  • Types of diagnostic testing
    • Stool culture → most sensitive but not clinically useful (slow turnaround time)
    • Cell cytotoxin assay → sensitivity of 67–100%; more expensive than EIA
    • Latex agglutination tests → low sensitivity (58–68%), high specificity (94–98%); not routinely utilized
    • Enzyme immunoassay (EIA) for toxin B &/or A → moderate sensitivity (63–94%), high specificity (75–100%); usually requires multiple samples, though this may not be cost-effective; utilized by majority of laboratories
    • Polymerase chain reaction (PCR) → high sensitivity & specificity; more expensive than EIA (testing of multiple samples not necessary due to high sensitivity)

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Clinical Pearl 33-1

Clinical suspicion is MOST important factor in diagnosis of C. diff infections, regardless of diagnostic testing

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Clinical Pearl 33-2

Repeat testing of stool during same episode not valuable as toxin may be present for weeks after resolution of infection

  • Drugs of choice → metronidazole (IV/PO) & vancomycin (PO) (Infect Control Hosp Epidemiol 2010;31:431)
  • Metronidazole & vancomycin comparable in mild-to-moderate infection; limited data suggest vancomycin superior in severe infection (Clin Infect Dis 2007;45:302)
    • Severe infection defined as ≥2 points: 1 point for age >60yo, temp >38.3°C, albumin <2.5mg/dL, WBC >15,000cell/mm3 & 2 points for pseudomembranous colitis or ICU admission
  • Severe, complicated cases (megacolon, perforation, acute abdomen, shock) may require colectomy (Infect Control Hosp Epidemiol 2010;31:431)
  • Fidaxomicin → not superior to vancomycin for treatment of initial infection but may lead to ↓ recurrences; extremely expensive (N Engl J Med 2011;364: 422)
    • Patient with multiple recurrences may benefit from a vancomycin taper/pulse regimen; e.g.:
      • 125mg PO QID × 10–14d → 125mg PO BID × 7d → 125mg PO daily × 7d → ...

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