Clostridium difficile

• Recent antibiotic use (any)
• GI surgery
• Severe underlying medical illness
• Chemo
• Elderly

• Viral (e.g. rotavirus)
• Bacterial
  • Campylobacter
  • Shigella
  • Salmonella (non-typhi)
  • Escherichia coli
    • E. coli 0157:H7
  • Yersinia enterocolitica
  • Vibrio cholerae
  • Clostridium difficile
• Parasitic
  • Giardia lamblia
  • Cryptosporidium
  • Entamoeba histolytica
  • Cyclospora
  • Microsporidium
• Toxin
  • Staphylococcus aureus
  • Bacillus cereus

• GI Bleed
• Appendicitis
• Mesenteric Ischemia
• Diverticulitis
• Adrenal Crisis
• Thyroid Storm
• Toxicologic exposures
• Antibiotic or drug-associated

• Enterotoxigenic E. coli (most common cause of watery diarrhea)[2]
• Norovirus (often has prominent vomiting)
• Campylobacter
• Non-typhoidal Salmonella
• Enteroaggregative E. coli (EAEC)
• Enterotoxigenic Bacteroides fragilis

• Giardia lamblia
• Cryptosporidiosis
• Entamoeba histolytica
• Cyclospora

• Consider testing patients with unexplained and new-onset ≥3 unformed stools within 24 hours[3]
• Institutions should have an agreed protocol using a stool toxin test as part of a multistep algorithm (e.g. glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT])
  • or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no preagreed institutional criteria for patient stool submission (Figure 2) (weak recommendation, low quality of evidence).

• C. diff toxin assay
  • Sn 63-94%, Sp 75-100%
• Culture
  • Positive culture only means C. diff present, not necessarily that it is causing disease

For patients with suspected Clostridium difficile associated diarrhea (CDAD)

• Low suspicion
  • Send stool for C. diff toxin assay
    • Positive → treat (no further testing indicated)
    • Negative → do not treat (no further testing indicated)
• High suspicion
  • Send stool for C. diff toxin assay AND treat empirically
    • Positive → treat (no further testing indicated)
    • Negative → Consider discussion with ID (false negative tests may occur); eval for other causes of diarrhea

• Never a need for repeat testing within 7 days of a previous test
• NO NEED to repeat positive tests as symptoms resolve as a “test of cure”
• NO NEED to repeat test soon after initial negative test (more likely to be a false positive test than a true positive test)

• Serum lactate levels >2.2 mmol/l
• Hypotension with or without required use of vasopressors
• Ileus or significant abdominal distention
• Mental status changes
• WBC ≥35,000 cells/mm3 or <2,000 cells/mm3
• Patient requiring ICU admission
• End organ failure (mechanical ventilation, renal failure, etc.)

• No diagnostic testing or treatment required[6]

• Either discontinue offending antibiotics (if possible) or give metronidazole 500mg PO q6hr x10-14d

• Vancomycin 125 mg PO four times daily
• Fidaxomicin 200 mg PO two times daily
• Metronidazole 500mg PO or IV q6hr x10-14d (third line therapy)

See criteria above (Evaluation section)

• Vancomycin 125-250mg PO q6hr x10d (IV form is not effective)
• Add Metronidazole 500mg IV q6hr if ileus or patient cannot tolerate PO
• Consider emergency colectomy if:
  • WBC >20K
  • Lactate >5
  • Age >75
  • Immunosuppression
  • Toxic megacolon
  • Colonic perforation
  • Multi-organ system failure

Relapse occurs in 10-25% of patients

• Occurs <=4 weeks after the completion of therapy
  • Otherwise consider other (more common) causes
• 1st recurrence: same agent as used to treat initial episode (antimicrobial resistance is not clinically problematic)
• 2nd recurrence: tapered vancomycin with pulse doses
• 3rd recurrence: PO vancomycin 10-14 days followed immediately by rifaximin "chaser" 400mg TID x20 days [7]
• Other options:
  • IVIG
  • Fecal transplant
  • Fidaxomicin 200mg BID x10 days noninferior to PO vancomycin, and reduces recurrences at 4 weeks after treatment (~15% vs 25%) [8]