CLOSTRIDIUM DIFFICILE Gram positive anaerobic bacillus - cytotoxin producing. Disease caused when toxin(s) bind to the surface of intestinal epithelial cells, where they are internalized and catalyze the glucosylation of cytoplasmic rho proteins, leading to cell death.
Typical occurs in elderly/instiutionalized especially after receiving antibioitics. Historically Clindamycin has been associated with high risk of C diff, in the Quebec outbreak in 2003, fluoroquinolone use was also associated with the development of infection. Direct person-to person spread occurs and previously healthy/younger/non institutionalized patients have also been infected.
PREVENTION
need responsible antibiotic use
infection-control measures (contact precautions, hand hygiene, environmental decontamination)
DIAGNOSIS
Microbiology
- C. diff toxin assay (EIA) detects toxins A and B and has ~70% sensitivity, with ~90-95% sensitivity on three tests. The specificity is> 95%.
- The most sensitive assay is the test for cytopathic effect, which is not available here
- You can also culture Clostridium difficile from the stool, but this is not routinely done, as there are nonpathogenic strains
- A positive toxin assay in a patient with minimal or no symptomsshould not prompt treatment. (i.e. only send for toxin testing if there is sufficient pre-test probability)
- Consider AXR to assess for toxic megacolon -a maximum colonic diameter greater than 6 cm is consistent with megacolon, may also see bowel wall changes
- CT scan helpful for further assessment and to R/O other causes of colonic distension etc.. May show thickening of the bowel wall, colitis, ileus
Sigmoid/Colonoscopy
Generally avoided with typical presentation and positive toxin EIA
Concern regarding endoscopy/insuflation of air causing perforation, especially if toxic megacolon present
May see pseudomembranes diagnostic of pseudomembranous colitis
Consider endoscopy if:
- Atypical presentation (ileus etc.)
- Other diagnoses suspected/need to be ruled out
- Failure of C. difficile infection to respond to therapy
See table from NEJM review here.
First Episode
***If possible stop offending antibiotics***
- Mild/Moderate Disease
- Metronidazole OR Vancomycin (PO) duration 10-14d
- Metronidazole OR Vancomycin (PO) duration 10-14d
- Severe Disease
- Defined as:
- Two of (Age above 60, Febrile, WBC above 15, Albumin below 25)
- OR hypotension/shock or Cr greater than 1.5x normal, or toxic megacolon, peritoneal signs, perforated bowel
- Two of (Age above 60, Febrile, WBC above 15, Albumin below 25)
- Infectious Disease +/- General Surgery Consultation
- ICU Consult for patients with hemodynamic comprimise
- Vancomycin (PO) unless severe illeus/toxic megacolon, then Metronidazole (IV) duration 10-14d (Vanco has more rapid symptom resolution and a lower risk of treatment failure).
- Defined as:
- First relapse --> can repeat last treatment depending on severity
- Second relapse --> vancomycin taper. ID consult.
NEJM Review article (2008) can be found here.
A paper discussing Vanco as first line treatment can be found here.
Thanks to Dr. T.C Lee for some of the above post.
