Treatment Guideline Chart
Clostridioides (formerly Clostridium) difficile infection is commonly associated with antibiotic treatment and is one of the most common nosocomial infections.
Symptoms usually start on days 2-3 of antibiotic treatment, but may also occur up to 8-12 weeks after discontinuation of antibiotics.
Discontinuation of antibiotics may be the only measure needed for patients with only mild diarrhea, no fever, no abdominal pain nor a high WBC count.
Cessation of antibiotics allows for reconstitution of the normal colonic microflora and markedly reduces risk of recurrence.

Clostridioides%20difficile%20infection Diagnosis

Laboratory Tests

  • Submitted stool specimens which are formed should not be used for laboratory testing  
    • There should be no recent initiation of enteral feeding or laxative use in the past 2 days 
  • When restrictions on sample submission are not implemented, multistep testing is recommended over single-step nucleic acid amplification tests (NAATs)   
  • Patients who are unable to produce stool specimens (eg those with ileus or toxic megacolon) may submit perirectal swabs for polymerase chain reaction testing 

Enzyme-Linked Immunoassay for Toxin 

  • Most common test used to detect C difficile toxins A and B
  • Has moderate specificity, rapid turnaround time (TAT), and is inexpensive but is not used alone due to its low sensitivity
    • Results are available within 2-6 hours
  • The test may need to be repeated in patients who initially had negative test results, but in whom C difficile infection is highly suspected

Glutamate Dehydrogenase (GDH)

  • Detects C difficile common antigen but does not differentiate between toxigenic and non-toxigenic strains 
  • Used as a screening tool for C difficile infection detection with good sensitivity but low specificity, has a rapid TAT, and is widely available and inexpensive

Nucleic Acid Amplification Tests (NAATs)

  • Detects C difficile toxin genes by identifying toxigenic organisms in the stool  
  • May be used alone or as part of a multistep testing when toxin and GDH tests are indeterminate 
    • False positives are of concern in single-step testing
  • Has high sensitivity but low to moderate specificity

Stool Cytotoxin Assay

  • Gold standard for the diagnosis of C difficile-mediated infection
  • Highly sensitive and specific
  • Disadvantages: Expensive, results only available after 24-48 hours, requires a tissue culture facility

Stool Culture

  • Not helpful in diagnosis because the test is not specific for pathogenic toxin-producing strains of C difficile
  • May be used for epidemiological typing and strain characterization

Other Laboratory Tests

White Blood Cell (WBC) Count

  • May show leukocytosis 

Blood Chemistry 

  • Eg serum creatinine, albumin, electrolytes 
  • May show electrolyte imbalance and evidence of dehydration
  • Serum lactate may serve as indicator of disease severity before performing surgical treatment

Stool Exam

  • Grossly bloody stools are rare, but occult blood may be present in severe colitis



  • Indications
    • If there is a delay or difficulty in lab tests for C difficile 
    • When lab exams for C difficile are negative but suspicion of the infection remains high 
    • When there is a need for rapid diagnosis, ie fulminant disease
    • In a patient who cannot produce stool because of ileus
    • As part of testing for other colonic diseases
  • The pseudomembranous finding on bowel mucosa or on examination of a biopsy sample is pathognomonic of C difficile colitis
  • Findings may be normal in mild disease or may show only nonspecific colitis in moderate cases
  • Sigmoidoscopy alone may not detect abnormalities when lesions are confined to the right colon
  • Colonoscopy and sigmoidoscopy may be contraindicated in patients with fulminant colitis because of the risk of perforation

Computed Tomography (CT) Scan

  • Not useful in confirming the diagnosis of early or mild colitis
  • May be used as a confirmatory procedure for suspected C difficile infection when thickening of colonic mucosa is seen
  • Can quickly diagnose fulminant disease
    • Abdominal and pelvic CT scan may be done in patients with complicated infection, ie abdominal distension with signs and symptoms of ileus or toxic megacolon
  • In cases involving the right colon, it may reveal bowel wall edema and inflammation


Stages of C difficile Infection

Non-severe Infection  

  • Diarrhea with mild abdominal pain and cramping 
  • Dehydration and electrolyte imbalance with mild to moderate infection 
  • Systemic inflammatory response symptoms (eg fever, fatigue)
  • WBC count <15,000/μL and serum creatinine <1.5 mg/dL

Severe Infection 

  • Diarrhea with increased abdominal pain and cramping including systemic inflammatory response symptoms 
  • Hypoalbuminemia <2.5 g/dL, WBC count ≥15,000/μL or serum creatinine >1.5 mg/dL and not caused by pre-existing comorbidities 

Fulminant Infection  

  • Hypotension or shock due to C difficile infection or 
  • Clinical and radiographic evidence of ileus not due to another disease process or toxic megacolon or 
  • Peritonitis on exam, radiographic finding of free air in abdomen and/or 
  • Colonic perforation 

Recurrent Infection 

  • C difficile infection meeting the above diagnostic criteria after initial resolution of symptoms following treatment completion and occurring within 8 weeks of prior episode or after new use of systemic antibiotic
  • 10-30% of patients with C difficile infection will experience a recurrent infection
  • Recurrences are not usually due to development of antibiotic-resistant organisms
    • Usually due to germination of persistent spores in the colon after treatment or reinfection because of reingestion of the pathogen 
  • Risk factors for recurrence include advanced age, severe infection or disease, immunocompromised state and concomitant use of other antibiotics for another infection

Multiply Recurrent Infection 

  • ≥2 recurrences of C difficile infection occurring after the initial episode with each episode meeting the above diagnostic criteria
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