Tuesday, March 28, 2017

Clostridium difficile Infection

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)


-          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).

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.