Clostridium difficile infection

• First recognized in 1978 as a cause of Antibiotic-Associated Diarrhea in 1978
• Clostridium difficile was reclassified as Clostridiodes difficile in 2016
• Initially included in genus Clostridium due to shared properties
• Later reclassified to be included in a completely different Bacterial family, Peptostreptococcaceae
• New genus was named Clostridiodes to preserve similar naming (C. Diff) and reduce clinician confusion
• Obligate, anaerobic, Gram Positive, spore-forming bacillus
• Causes Secretory Diarrhea and mucosal injury with colitis
• of virtually any antibiotic may lead to C. difficile infection

Risk Factors

• Highest risk patients
  • Older patients over age 64 years old, and especially over age 70 years
    • Risk of C. difficile infection increases 2% for each year over age 18 years old
  • Debilitated patients
  • Immunocompromised patients
    • Includes Hematopoietic Stem Cell Transplant and Solid Organ Transplant
    • Includes Corticosteroid use
  • Cystic Fibrosis patients (high risk for fulminant infection)
  • Obesity
  • Female Gender
  • Chronic Kidney Disease (esp. Serum Creatinine >2)
  • Gastrointestinal conditions
    • Enteral feeding
    • Gastrointestinal surgery
    • Small Bowel Obstruction or Adynamic Ileus
    • Inflammatory Bowel Disease
    • Cirrhosis
    • Malnutrition or low Serum Albumin
  • Acid suppression
    • Proton Pump Inhibitors (e.g. Omeprazole)
      • Highest risk as they raise gastric pH most significantly
    • H2 Blockers (e.g. Ranitidine)
      • Less risk than with Proton Pump Inhibitors
  • Recent antibiotic use within last 3 months (especially last 7-10 days)
    • General
      • All antibiotics can cause C. difficile Diarrhea (even single dose perioperative antibiotics)
      • Broad-spectrum agents are highest risk
      • Risk increases with combination antibiotic regimens, frequent dosing and longer therapy duration
      • Up to 40% of C. difficile are in patients without recent antibiotic use
    • Most common antibiotic causes
      • Clindamycin
      • Fluoroquinolones (e.g. Ciprofloxacin, Levofloxacin)
      • Broad-spectrum Cephalosporins
      • Ampicillin or Amoxicillin (most common cause in United States)
      • Macrolides (e.g. Erythromycin, Azithromycin)
      • Carbapenems (Ertapenem)
    • Less common antibiotic causes
      • Tetracycline antibiotics (e.g. Doxycycline)
      • Sulfonamides (e.g. Bactrim)
      • Trimethroprim
    • Rare antibiotic causes
      • Parenteral Aminoglycosides
      • Metronidazole (used for treatment)
      • Vancomycin (used for treatment)

Symptoms

• Asymptomatic carrier state is common
  • Megacolon may be present without Diarrhea
• Inflammatory Diarrhea (variably present)
  • Timing
    • Incubates for 2-7 days after colonization
    • Most cases occur on days 4-9 of antibiotic course
    • Onset <14 days after antibiotics in 96% of cases
    • All cases occur within 3 months of antibiotics
  • Characteristics
    • Frequent, watery Bowel Movements to profuse Diarrhea up to 20-30 stools daily
    • Foul, characteristic odor may be present, but not shown in studies to be sensitive or specific
    • Mucus and occult blood often present
    • Acute inflammatory symptoms (<50% of cases)
      • Fever (>38.5 C in 15% of cases)/Crampy Abdominal Pain/Decreased appetite/Malaise/Nausea or Vomiting may be present in 2 to 30% of patients
• In severe cases, Pseudomembranous colitis and toxic Megacolon occurs

decrease the incidence of C. difficile by

• Avoiding inappropriate antibiotic therapy 
• When antimicrobials are indicated, using the narrowest-spectrum drug for the shortest period is essential. 
• Antimicrobial stewardship programs using consensus guidelines
• antimicrobial pre-approval
• directed therapy based on culture results (where possible)
• limiting the duration of intravenous and oral antimicrobials