Clostridium Difficile: be on the lookout!

This is a cause of diarrhea that you don't want to miss!

C. difficile: this organism colonizes the intestinal tract after the normal gut flora have been altered by antibiotic therapy! It is one of the most common healthcare-associated infections and can have detrimental effects, particularly in the elderly

Disease Spectrum: ranges from asymptomatic carrier state to severe fulminant disease with toxic mega-colon      

• Carrier: 20% of adults in hospital are “carriers” who shed C. difficile in their stools, but do not have diarrhea. The rate of “carriers” is higher in long-term care facilities, creating a reservoir for contamination.
• C. difficile associated diarrhea (CDAD): watery diarrhea (i.e. 10-15 BM/day), cramping, lower abdominal pain and low-grade fever. Often accompanied by leukocytosis

Antibiotics: the most common culprits that create a pre-disposition to CDAD include clindamycin, fluroquinolones, clindamycin, cephalosporins, and penicillin.

Physical Exam: lower abdominal tenderness. Signs of volume depletion may be noted.

Imaging: CT abdomen in the setting of pseudomembranous colitis, demonstrates thickened colonic wall

Endoscopic Findings: shallow-ulcers may be noted on the mucosal surface of the intestine. The ulcers allow for release of mucous, inflammatory cells and proteins; these manifest grossly on the mucosal surface as “pseudomembranes.” These pseudomembranes are raised yellow or light coloured plaques; they are essentially pathognomonic for C. diff infection. The scope may also demonstrated friable bowel with erythema or bowel wall edema.

Complications

• Disease recurrence and/or re-infection: develops in 10-25% of patients
•  Fulminant colitis, which may lead to Toxic Megacolon
• Toxic Megacolon: bowel dilatation (>7 cm in its greatest diameter), with evidence of associated toxicity.
• Bowel perforation
•  Extra-colonic involvement (rare): small bowel involvement, reactive arthritis, appendicitis, etc

Making the Diagnosis

Need moderate-to-severe diarrhea or ileus and either:

•   Stool test: positive for C. difficile toxins or toxigenic C. difficile
•  Endoscopic or histologic findings of pseudomembranous colitis

-Consider C. diff in patients with >2-3 loose, watery BM per day for at least two days

-Diagnosis: C. difficile toxin (s) or toxigenic C. difficile organisms

•  PCR (Preferred, as it is very sensitive & specific, with results available quickly!)
•  Enzyme immunoassay (EIA) for C. diff GDH (cannot distinguish b/w toxigenic and non-toxigenic strains)
• EIA C. diff toxins A &B (sensitivity 75%, specificity up to 99%)

Management- Broad Principles

•  Discontinue any non-essential antibiotics and practice excellent antibiotic stewardship (i.e. always step-down to more narrow antibiotics once the susceptibilities are back on cultures for any infection!)
•  Infection control policies (contact precautions), washing hands with soap and water (may be more effective than EtOH-based hand sanitizers in removing C. diff spores)
• Monitor electrolytes, volume status, fluid losses, etc

Specific Therapy

Non-severe disease, initial therapy

·       Metronidazole (Flagyl) 500 mg PO TID x 10-14 days

o   Side effects: dose-dependent peripheral neuropathy, nausea

o   Risks: may be slightly less efficacious than vancomycin *(more literature required)

·       Vancomycin 125 mg PO QID x 10-14 days

NOTE: ~50% of patients have positive stool cultures assays for up to 6 weeks after completion of therapy. Thus, do NOT repeat the stool culture a few weeks after therapy if the patient is clinically well!!

Re-infection & Disease Relapse

A large proportion of these cases are actually re-infections rather than relapses. Recurrence occurs in up to 25% of those treated initially (i.e. with flagyl or vancomycin). These recurrences generally occur within 1-3 weeks after completion of antibiotics. Risk factors for recurrence include: age >65 years, severe underlying medical conditions, and the need for ongoing antibiotics during treatment.

Initial recurrence: consider a course of Vancomycin or Fidoxamicin

Subsequent Recurrence: consider vancomycin in a pulse tapered fashion, Fidaxomicin or Rifaximin +/- probiotics

Fecal Bacteriotherapy: something to consider! Only done at certain centers

Severe Infection

-Suggestions of severe infection: WBC >15, AKI (Cr> 1.5x baseline), complications (i.e. shock, toxic mega-colon)

-Treatment: guidelines from the IDSA recommend vancomycin (oral) as the first line therapy for severe C. diff infection.

·         Major advantage of vancomycin vs. flagyl: Vancomycin allows for more maximal concentrations of the drug to act intra-colonically. Prescribe Vancomycin 125 mg PO QID

·       
          If these patients with severe disease on vancomycin fail to improve clinically, consider Fidaxomicin

Non-Antibiotic Management

•   Surgical intervention: may be required in severe cases, or those with perforation, necrotizing colitis, or toxic megacolon
• Consideration of probiotics
• Anion-binding resins: consideration for the future (i.e. tolevamer)
• IVIG: described for refractory, severe cases in some case-report literature

Resource:

NEJM (2011): Fidaxomicin versus Vancomycin for Clostridium difficile Infection