What is the main symptom associated with a C. Difficile infection?
Clostridioides difficile associated diarrhea (CDAD)
What are some signs of a C. difficile infection?
- More than 3 unformed stools per 24h and more than 2 days with no other recognized cause
- Detection of toxin A or B or C. difficile in stool
- Pseudomembranes in the colon
- Patients with recent antibiotic use (within the previous 3 months)
What are the clinical manifestations of C. difficile infections?
- Diarrhea (almost never grossly bloody or purulent)
- Fever (28% of cases)
- Abdominal pain (22%)
- Leukocytosis (50%)
- Mild diarrhea to life-threatening toxic megacolon
What are the steps of pathogenesis for C. difficile?
Step 1: Exposure to antimicrobial agents establishes susceptibility to C. diff thrigh disruption of normal colonic microbiota
Step 2: Exposure to toxigenic C. diff (can be carried asymptomatically)
Step 3: Virulent strain or high risk antibiotic or inadequate host immune response
What is the most common environment where a patient can become colonized with C. difficile?
Acquired exogenously (most often in hospital or nursing homes
What are some characteristics of the C. difficile bacteria?
- Gram positive
- Spore forming
- Anaerobic bacillus
- Causes toxin mediated disease (toxins A and B)
How is diagnosis of C. difficile infection confirmed?
Presence of Toxins A and B
Which antibiotics cause C. difficile infections?
All antibiotics have been associated with C. difficile infections
Which antibiotics are associated with higher risk of C. difficile infections?
- Clindamycin
- Fluoroquinolones
- Cephalosporins (3rd and 4th gen in particular)
- Ampicillin
- Carbapenems
Which antibiotics are associated with lower risk of C. difficile infections?
- Penicillin
- Macrolides
- Tetracyclines
- TMP/SMX
- Aminoglycosides
How long does the risk of C. difficile infection last after stopping antibiotic therapy?
3 months past therapy
What are some risk factors associated with C. difficile infections?
- Older age
- Greater severity of underlying illness
- GI surgery
- Use of rectal electronic thermometers
- Enteral tube feeding
- Antacid therapy (PPIs higher risk than H2RAs)
- Hospitalization
Are recurrent C. difficile infections common?
- 15-30% of patients experience recurrence after their first infection
- Recurrences are either relapses (same strain) or new infection (new strain)
How are C. difficile infections managed?
- Stop the offending antibiotic if possible (need to make clinical judgement)
- Fluid and electrolyte replacement therapy (concerned about dehydration)
- Avoid antimotility drugs (ex. loperamide)
- Categorize as mild-moderate to severe and uncomplicated to complicated
What patient factors qualify a C. difficile infection to be severe?
Elevated WBC (leukocytes are over 15 thousand/microlitre) and/or SCr over 1.5x baseline
What patient factors qualift a C. difficile infection to be complicated?
In addition to standard C. difficile symptoms, the patient may have one of the following:
- Hypotension
- Shock
- Ileus (patient is refusing oral food due to slow GI motility)
- Megacolon (can occur when C. difficile excessively builds up in the colon)
What is the first line treatment option for mild-moderate and uncomplicated C. difficile?
Vancomycin 125mg PO QID for 10-14 days
What are some alternative treatments for mild-moderate and uncomplicated C. difficile?
- Fidaxomicin 200mg PO BID for 10 days
- Metronidazole 500mg PO TID for 10-14 days (used when costs of vancomycin or fidaxomicin are prohibitive)
What are the treatment options for severe uncomplicated C. difficile?
- Vancomycin 125mg PO QID for 10-14 days
- Fidaxomicin 200mg PO BID for 10 days
What are the treatment options for severe complicated C. difficile?
- Vancomycin 125-500mg PO QID for 10-14 days or via NG tube in conjuction with metronidazole 500mg IV q8h
- Vancomycin retention enema sometimes added if ileus
- Alt: Fidaxomicin 200mg PO BID for 10 days with IV metronidazole if patient has severe allergy to PO vancomycin
What is the treatment option for the first recurrence of C. difficile?
It is the same treatment as initial episode
- Vancomycin 125mg PO QID for 10-14 days
- Fidaxomicin 200mg PO BID for 10 days
What is the treatment option for second and subsequent recurrences of C. difficile?
Vancomycin as a prolonged taper and/or pulsed regimen
Taper can last for over a month
What is fecal microbiota transplantation?
A fecal sample from a relative with normal GI microflora is put into the C. difficile patient
- Amazing success rates so far (rare cases of pathogen transmission)
What is the role of monoclonal antibodies in C. difficile treatment?
These monoclonal antibodies bind to toxin
Toxin A - actoxumab
Toxin B - bezlotoxumab
