During morning
report we discussed a case of Clostridium
difficile Infection (CDI). Here are some key points about the risk factors,
diagnosis, risk stratification, and management of CDI.
Pathophysiology and Risk factors:
-
Clostridium
difficile is an anaerobic Gram-positive spore-forming bacillus
-
Transmitted
through the fecal-oral route by spores
that are resistant to heat, acid, and antibiotics
-
Colonizes
the large intestine and makes exotoxins that cause colitis in susceptible
patients
-
In
a healthy host, colonization is prevented by barrier properties of a health
fecal microbiota
-
Most
of the risk factors for CDI have to do with a weakened fecal microbiota
-
Risk
factors:
o
Antibiotics
(Most important risk factor!)
§ Almost all antibiotics are a risk
factor but classically think of fluoroquinolones, cephalosporins, clindamycin,
ampicillin and amoxicillin (1)
§ Interestingly, a recent cohort study
in JAMA Internal Medicine, showed that even the receipt of antibiotics by prior
hospital bed occupants can increase the risk for CDI in subsequent patients who
occupy the same bed! (2)
o
Advanced
age
o
Chemotherapy
o
Underlying
diseases (such as inflammatory bowel disease, immunosuppression) (1)
Diagnosis:
-
The
diagnosis of CDI is usually made by C diff toxin assays in stool (either an
enzyme immunoassay for toxins or a PCR test for microbial toxin genes)
-
Culturing
Clostridium difficile in stool is not
widely available and is not often used
-
Note
that the C diff toxin assays may stay positive after a CDI is appropriately
treated so a positive C diff stool test after an appropriate course of
treatment for CDI needs to be interpreted with caution (i.e. involve the
expertise of Infectious Disease)
Risk stratification and management:
-
How
one treats CDI varies depending on the severity of the infection.
-
One
resource I find very helpful is the Antimicrobial Stewardship Program of
UHN/SHS best practices:
-
This
is their summary slide on C difficile
severity Criteria:
-
And
here is a summary of the treatment of CDI based on severity:
-
-
Bottom
line is that metronidazole is first-line for mild-moderate disease and ORAL
vancomycin is first line for severe disease. Once there is
complicated/fulminant disease, ORAL vancomycin and IV metronidazole are both
given and General Surgery and Infectious Diseases consultations are key.
-
Keep
in mind that the vancomycin needs to be given ORALLY! It is not absorbed in the
GI tract and therefore will act in the colon where the infection is; IV
vancomycin isn’t going to help.
-
There
are subtleties to the treatment of recurrent CDI including much interest in fecal
microbial transplantation, which has evidence supporting its effectiveness and
cost-effectiveness in the treatment of recurrent CDI, including RCTs (4).
References:
1. NEJM review article: Leffler D,
Lamont JT. Clostridium difficile infection.
N Engl J Med. 2015;372(16):1539. http://www.nejm.org/doi/pdf/10.1056/NEJMra1403772
2. Freedberg et al. Receipt of antibiotics
in hospitalized patients and risk for Clostridium difficile infection in
subsequent patients who occupy the same bed. JAMA Intern Med.
2016;176(12):1801-1808.
3. Antimicrobial Stewardship Program of
UHN/SHS best practices: http://www.antimicrobialstewardship.com/antimicrobial-stewardship-best-practices
4. Health Quality Ontario. Fecal
Microbiota therapy for Clostridium difficile infection: A health technology
assessment. Ont Health Technol Assess Ser. 2016; 16(17):1-69.
