Clostridioides difficile Infection (CDI) Flashcards
C. diff microbiology basics
gram-positive, spore-forming, obligate anaerobic bacillus - produces 2 toxins (TcdA, an inflammatory enterotoxin and TcdB, cytotoxin)
included in normal flora in small percentage of healthy individuals - colonization higher in hospitalized patients
How is C. diff transmitted?
transmitted person to person via fecal-oral route through ingestion of spores
healthcare associated on hands of personnel and contaminated surfaces
What are the risk factors for C. diff?
antibiotic exposure, healthcare exposure, age >/= 65 years, proximity to person with C. diff infection, use of acid suppressing agents (PPI, H2RA), chemotherapy, immunosuppression, GI surgery
What are the highest risk antibiotics?
fluoroquinolones, clindamycin, 3rd/4th gen cephalosporins, carbapanems
What is the infection pathogenesis of C. diff?
- Disruption of the colonic microflora: Gut microbiome suppresses C. difficile colonization, overgrowth, and toxin production
- Source and introduction of C. difficile to the colon (if not already colonized)
- Multiplication of C. difficile occurs and toxin production begins
- Colon and rectal mucosa becomes edematous, erythematous with adherent, raised plaque-like pseudomembranes (yellow-white): Occurs throughout the colon, most prominent in rectosigmoid area
What are the signs and symptoms of C. diff infection?
Two primary symptoms:
▪Profuse, watery or mucoid green, foul-smelling diarrhea
▪Abdominal pain
Additional signs and symptoms:
▪Fever
▪Leukocytosis
▪Hypoalbuminemia
▪Acute kidney injury
When should you test for C. diff infection?
3 or more profuse, watery or mucoid green, foul-smelling stools in 24 hours
Not recommended to test asymptomatic patients or samples with formed stool
What are the testing methods utilized for the most sensitive results?
- Nucleic acid amplification test (NAAT) alone (in conjunction with signs/symptoms)
- Antigen test (GDH) + Toxin A/B test (NAAT used to resolve discordant results)
- NAAT + Toxin A/B test
Should we repeat test?
Repeat testing within 7 days of same episode of diarrhea has limited value and is not recommended
What are the classifications of severity of C. diff?
non-severe, severe, and fulminant
What are the characteristics of non-severe C. diff?
WBC ≤ 15,000/mcL
SCr < 1.5 mg/dL
What are the characteristics of severe C. diff?
WBC > 15,000/mcL
SCr > 1.5 mg/dL
What are the characteristics of fulminant C. diff?
Hypotension or shock Ileus
*Toxic megacolon - considered a medical emergency and involves severe inflammation in the colon. Surgical intervention is necessary, and mortality is high (~50%).
What are the treatment options for C. diff?
oral vancomycin
fidamoxicin
metronidazole
What are the pros of oral vancomycin
- Broad spectrum coverage
- Standard of care
What are the pros/cons of fidaxomicin?
- Narrower spectrum
- Higher rates of sustained response
What are the pros of metronidazole (IV or PO)
- No longer recommended as first-line agent
- Reserved for fulminant cases as additional agent
What are PK/PD considerations for oral vancomycin?
▪Extremely poor oral absorption (Since oral vancomycin is minimally absorbed from the gastrointestinal (GI) tract, it remains in the intestines, achieving high local concentrations directly at the site of infection — the colon. This makes it effective for targeting C. difficile bacteria, which primarily cause infection in the colon)
▪C. difficile infection only indication for oral vancomycin use
What are patient focused considerations for oral vancomycin?
▪Liquid version can have bitter taste ▪Cost considerations
⎻ Typically covered by insurance for manageable copay
⎻ Liquid version often requires prior authorization and is more costly
What are PK/PD considerations for fidaxomicin?
▪Protein synthesis inhibitor
▪Extremely poor oral absorption
What are patient focused considerations for fidaxomicin?
▪Higher rates of sustained treatment response and lower recurrence rates ▪Cost considerations
⎻ Cost is biggest barrier for use – Acquisition cost ~$4,500
⎻ Insurance coverage increasing, but often requires prior authorization
What are PK/PD considerations for metronidazole?
▪Excellent oral absorption (> 90%)
What are patient focused considerations for metronidazole?
▪Less efficacious and higher risk for recurrence ▪Cost considerations
⎻ Least costly option
What are the treatment recommendations for C. diff infection for initial episode, non-severe?
Fidaxomicin 200 mg PO Q12H x 10 days
Vancomycin 125 mg PO Q6H x 10 days
Metronidazole 500 mg PO Q8H x 10 days - Only use if other options unavailable/unfeasible
What are the treatment recommendations for C. diff infection for initial episode, severe?
Fidaxomicin 200 mg PO Q12H x 10 days
Vancomycin 125 mg PO Q6H x 10 days
avoid peristatic agents (loperamide)
What is the general treatment approach with recurrent CDI?
▪Change something – either the drug or dosing regimen
What are the treatment recommendations for C. diff infection for first CDI recurrence?
Fidaxomicin 200 mg PO Q12H x 10 days - If not used for initial episode
Vancomycin 125 mg PO Q6H x 10 days - If not used for initial episode
Fidaxomicin 200 mg PO Q12H x 5 days, then 200 mg PO every other day x 20 days (extended dosing)
Vancomycin tapered and pulsed regimen
What are the treatment recommendations for C. diff infection for 2nd and subsequent CDI recurrence?
One of the above options, select a different treatment strategy than previous recurrences
avoid peristaltic agents (loperamide)
What are the treatment recommendations for C. diff infection for fulminant CDI?
this is in order of preference:
Vancomycin 500 mg PO Q6H Plus
Metronidazole 500 mg IV Q8H
If ileus present, consider adding vancomycin 500 mg via rectal instillation Q6H
Treatment duration not as well defined
avoid peristaltic agents (loperamide)
What are the risk factors for CDI recurrence?
age >/= 65yo
immunocompromised host
severe CDI on presentation
What is fecal microbiota transplant?
FMT basics
▪Administration of fecal material from healthy person to restore a balanced gut microbiome ▪Utilized as both a treatment option and method to reduce recurrence
What are potential indications for fecal microbiota transplant?
▪Three or more episodes of CDI
▪Poor response to initial antibiotic therapy for CDI
What are patient-focused considerations for fecal microbiota transplant?
▪Requires administration via endoscopy, colonoscopy, or rectal tube
▪Not available at all hospitals
What are examples of fecal microbiota transplants?
rebyota
vowst
What is rebyota and when is it indicated to use?
▪Fecal microbiota suspension
▪Prevention of recurrence of CDI for patients following antibiotic treatment for recurrent CDI
What are patient-focused considerations for rebyota?
▪Requires administration via rectal tube
▪Cost considerations – ~$9,100 per dose
What is vowst and when is it indicated to use?
▪Bacterial spore suspension
▪Modulate bile acid concentrations and restore fatty acids, which results in resistance to C. difficile colonization and restoration of the gut microbiome
▪Prevention of recurrence of CDI for patients following antibiotic treatment for recurrent CDI
What are patient-focused considerations for vowst?
▪Oral option!
▪Cost considerations – ~$18,500 per course
▪Side effects – abdominal distention, fatigue, constipation, chills, diarrhea
What is bezlotoxumab and when is it indicated for use?
▪Monoclonal antibody targeting C. difficile toxin B to neutralize its effect
▪Prevention of recurrence of CDI for patients at high risk for CDI recurrence
What are patient-focused considerations for bezlotoxumab?
▪Caution in patients with CHF (↑ risk of CHF and mortality?)
▪Cost considerations – ~$3,800 per dose
Do we use probiotics in CDI?
controversial!
Insufficient data for CDI prevention
Potential risk for bloodstream infection
Many antibiotics kill bacteria in probiotics
If you have a history of CDI, what should you do if you need antibiotics again?
▪Oral vancomycin prophylaxis has been studied
▪Common dose is vancomycin 125 mg PO Q12H during and for 3-5 days after completion of
antibiotic therapy
▪Current studies are limited by retrospective designs and small patient population
▪Unclear what effect this can have on normal gut microbiome and future CDI recurrences
