Clinical Background
Clostridium difficile is the major cause of antibiotic-associated diarrhea (AAD) and pseudomembranous colitis (PMC).
Epidemiology
- Incidence – 112/100,000 in U.S. for adult Clostridium difficile-associated disease (CDAD) hospitalizations (CDC, 2005)
- C. difficile causes 15-25% of all AAD and more than 90% of documented cases of antibiotic-associated PMC
Organism
- Gram-positive, spore-forming rod
- Obligate anaerobe
- Produces toxins – A, B and binary
- Toxin production is necessary to produce disease
- A and B activate cytokines
- Binary toxin is less well understood – produced by NAP1 strain (NAP1/B1/027); this strain also produces A and B toxins in much higher quantities than other strains; may be a hypervirulent strain
- Cultured from the stool of up to half of healthy neonates (<1 yr), 3% of healthy adults and 35% of hospitalized patients
Risk Factors
- Antimicrobial administration within previous 60 days – >90% of cases have this risk factor
- Age >65 years
- Previous history of C. difficile disease
- Prior or current hospitalization
- Residence in long-term care center
- Severe underlying illness
Clinical Presentation
- Asymptomatic carrier state
- Mild – non-bloody diarrhea, abdominal cramping, >3 stools/day
- Severe – abdominal pain, severe diarrhea, fulminant disease (toxic megacolon and paralytic ileus) with fever, anorexia, nausea and malaise
- Recurrent disease (15-25% of patients)
- Typically occurs within 4 weeks of completion of therapy
Treatment
- Often difficult to eradicate
- In symptomatic patients, treatment is usually necessary
Diagnosis
- Indications for testing
- Severe or persistent diarrhea in patients with risk factors (predominantly previous antibiotic use); may occur up to several months after antibiotic use
- Laboratory testing
- Initial testing
- CBC – often demonstrates leukocytosis; if leukocytosis not present, may want to rule out other organisms as the cause of diarrhea
- Culture stool for Campylobacter, Salmonella, Shigella, E. coli (Shiga toxin producing strains)
- Testing for presence of toxins A and B (multiple repeats in 24-hour period are not recommended); should not be used to monitor therapy.
- Cytotoxin cell assay – may require 48 hours for results
- Enzyme immunoassay (EIA) – rapid but less sensitive than cytotoxin cell assay (sensitivity ~80% for stool specimen)
- PCR of stool for presence of cytotoxin genes
- Emerging gold standard; rapid platforms available
- Requires up to 72 hours
- Does not distinguish toxin-producing strains; isolates should be tested for toxin production
- Individuals without disease may have positive culture; perform only in symptomatic patients
- Useful for epidemiological purposes
- Endoscopy – classic exam effectively demonstrates pseudomembranous colitis but sensitivity is low (50%) for CDAD
Differential Diagnosis
- Other bacterial diarrhea
- Diarrhea, viral evaluation
- Diarrhea, parasitic evaluation
- Inflammatory bowel disease
Pharmacogenetics and Therapeutic Drug Monitoring
Indications for Laboratory Testing
- Tests generally appear in the order most useful for common clinical situations
- Click on number for test-specific information in the ARUP Laboratory Test Directory
| Test Name and Number |
Recommended Use |
Limitations |
Follow Up |
| Clostridium difficile Cytotoxin Cell Assay 0060851 Method: Cell Culture Assay/Confirmation by Anti-Toxin Neutralization |
Use for clinically relevant diagnosis; test is the most specific and is highly sensitive |
May take up to 48 hours to get results |
|
| Clostridium difficile Toxins (A & B) by EIA 0065146 Method: Enzyme Immunoassay |
Use for rapid and clinically relevant diagnosis; test is less sensitive (70-90%) than culture or cell assay |
False negative results are common |
|
| Clostridium difficile Culture with reflex to Cytotoxin Cell Assay 0060140 Method: Standard reference procedures for anaerobic bacterial culture and identification |
Use for epidemiological purposes, such as strain typing during suspected outbreak |
Culture alone does not distinguish toxin-producing strains Requires up to 72 hours for report |
|
Guidelines
General References
Comprehensive Review: November 2009
Last Update: November 2009