Etiology

• Nosocomial, or hospital acquired diarrhea, is defined as acute development of >3 loose stools in a day after 3 or more days of hospitalization.
• Community-acquired causes of diarrhea (e.g. viral or bacterial diarrhea) are unlikely to develop after 3 days of hospitalization.
• Most commonly patients develop non-bloody diarrhea, which is often due to:
  • Medications:
    • Antibiotics (independent of their ability to facilitate C. difficile infection).
    • ARVs.
    • NSAIDs.
    • Antidepressants.
    • Antipsychotics.
    • Anti-epileptics.
    • Anti-arrhythmics.
    • Medications containing magnesium, potassium, or sorbitol.
  • Clostridium difficile infection (CDI).
  • Enteral feeding.
  • Underlying illnesses.
• Less common causes include other infectious agents, opioid withdrawal, malabsorption (from tube feeds and lactose-containing supplementation or pancreatic insufficiency due to pancreatitis), and hyperthyroidism.
• A very constipated patient (older, on opioids) can have overflow diarrhea around a fecalith.

Evaluation

• Send stool sample for C. difficile testing. In general, toxin positivity = infection; PCR positivity may indicate colonization.
  • Only send if 3+ unformed stools in 24 hours (asymptomatic carriage of C. diff is common).
• Stool cultures and ova and parasites should be sent in immunocompromised patients and individuals with inflammatory bowel disease.
  • If high suspicion (e.g., HIV+), collecting multiple samples (3+) increases diagnostic yield.
• In patients who develop diarrhea after being hospitalized for more than 3 days (>72 hours), cause is usually nosocomial; there is low utility in sending stool ova and parasites and stool cultures.
• Routine stool cultures do not test for Giardia, Cryptosporidium, Entamoeba, Microsporidia species, and E. coli O157:H7, so request these studies if there is increased clinical suspicion (e.g. immunocompromised patients, bloody diarrhea).
• If pancreatic insufficiency is suspected, send fecal fat testing to check for malabsorption.
• Consider consulting GI for:
  • Bloody diarrhea.
  • If studies are negative and diarrhea persists.
  • Have a lower threshold for consultation if the patient is immunocompromised, has suspected IBD, or recurrent or severe CDI.

Management

• Discontinue offending medication, if possible.
• Do not use anti-motility agents initially; if diarrhea is secondary to C. diff, retention of toxin can precipitate toxic megacolon.
• Once C. diff infection has been ruled out, anti-motility therapy includes:
  • Loperamide (4mg initially followed by 2mg with each stool, max 16mg/day).
  • Lomotil.
• Bismuth subsalicylates can help control mild diarrhea and is overall fairly benign.
• Consider changing TF formulation.
• There is no therapeutic role for probiotics. However, probiotics may be considered for prevention of CDI associated with antibiotic use.

Clostridium difficile Infection

• Clinical presentation:
  • Diarrhea (typically non-bloody).
  • Abdominal discomfort.
  • More severe infection:
    • Leukocytosis (particularly over 15,000).
    • Fever.
    • Abdominal distension / ileus.
    • Signs of peritonitis.
  • Lack of diarrhea is rare, but possible (1-2% of all cases).
• Risk factors:
  • Current or recent antibiotic use (higher risk antibotics include penicillins, cephalosporins, clindamycin, fluoroquinolones).
  • Prior C. diff infection.
  • Advanced age.
  • Immunosuppression.
  • Chemotherapy.
  • IBD.
  • Nursing home residence.
  • Recent hospitalization.
• IDSA Clinical Practice Guidelines suggest the following for treatment of an initial episode of CDI:

• Discontinue other antimicrobials as soon as possible, as this may increase the risk of CDI recurrence.
• Meticulous hand washing and contact precautions with gloves and gown are vital to minimize spread of this organism. Alcohol-based hand gels are NOT effective in killing C. diff spores.
• Contact precautions should be maintained until stool is formed for 24h.
• Toxin assay can remain positive for several weeks, no utility in repeating assay after treatment.

Recurrent Clostridium difficile Infection (CDI)

• Recurrence (up to 20% after first course of treatment and then approximately 50% after subsequent treatments) is due to re-ingestion of spores or spores remaining in the GI tract after therapy. 
• Antibiotic resistance has been reported but is rare.
• First recurrence: vancomycin pulsed/tapered OR fidaxomicin.
• Second recurrence: vancomycin pulsed/tapered OR fidaxomicin OR vancomycin + rifaximin OR fecal microbiota transplant.
• No current role for probiotics.
• There is no evidence to support the use of cholestyramine or rifampin as adjunctive therapy.

Fehér et al., A Comparison of Current Guidelines of Five International Societies on Clostridium difficile Infection Management. Infect Dis Ther. 2016 Sep; 5(3): 207–230.

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Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013; 368:407.