2 - Clostridium Difficile Infection Flashcards
What is clostridium difficile?
- Anaerobic
- Spore forming
- Exotoxin-producing
- Gram pos bacteria
How is C. diff transmitted?
Fecal-oral route
What causes the sx of CDI?
Enterotoxin A and cytotoxin B
NAP1 is associated w/ _______
Fluoroquinolone use
What is the significance of NAP1 C. diff strain?
- Hyper-virulence due to hyper-production of C. perfringens-type toxin
- Higher rates of tx failure, recurrence, complications and attributable mortality compared w/ non-NAP1
Over ___% of CDI associated w/ NAP1
30%
What are the risk factors for CDI?
- Antimicrobial therapy that disrupts normal colonic flora, typically presents w/in 4-9 days
- Previous CDI
- Hospitalization > 72 h
- Female, advanced age (65 and older)
- Multiple co-morbidities, severe underlying disease, immunocompromised
- Gastric acid suppression, enteral feeding, GI surgery, inflammatory bowel disease
Which antibiotics are associated w/ CDI?
- Highest risk = clindamycin
- High risk = fluoroquinolones (NAP1), cephalosporins, penicillins
- Moderate risk = macrolides, sulfonamides
- Low risk = tetracyclines, aminoglycosides
Clinical signs of CDI
- Watery diarrhea w/ 3 or more unformed stools in 24 h
- N/V, abdominal pain, high fever, significant leukocytosis
Normal WBC levels
4.5-11 * 10^9 cells/L or 4,500-11,000 cells/uL
Normal neutrophils levels. When do they increase?
- 1.8-5.2
- Increase significantly during bacterial infections
Normal lymphocyte levels. When do they increase?
- 1.3-3.2
- Increase during viral infections
Normal monocyte levels
0.3-0.8
When do eosinophil levels increase?
Parasite infection or allergies
Complications of CDI
- Most common = recurrence
- Septic shock
- Pseudomembranous or fulminant colitis
- Ileus
- Toxic megacolon (gut is immobile and expands)
- Perforation
How is CDI diagnosed?
- GI sx w/ diarrhea and positive C. difficile toxin in stool
- Stool culture and molecular typing during outbreaks
What is the sensitivity and specificity of the C. difficile assay?
- Sensitivity = 75-80%
- Specificity is very high, so false positives are very rare
Strategies for preventing CDI
- Infection control
- Antimicrobial stewardship for clindamycin, fluoroquinolones, and other high-risk agents
- Probiotics
What can be done to prevent the spread of CDI?
- Environment cleaning and disinfecting
- Healthcare worker hygiene, handwashing (alcohol-based sanitizers not effective against spores)
- Contact and barrier precautions when known or suspected CDI
- Single pt rooms for those w/ known CDI
General approach to treating CDI
- Discontinue offending antimicrobial if possible, or replace w/ lower-risk agent (controversial)
- Supportive measures for hydration and electrolyte balance
- Avoid anti-motility agents
- Antimicrobial therapy for CDI
- Infection control measures
- Surgery for severe, complicated disease
Tx for non-severe CDI
- Metronidazole 500 mg po/ng q8h x 10-14 days (w/ at least 7 days beyond d/c of offending agent)
- Switch to vanco if tx failure
What is the response and recurrence rate to metro for non-severe CDI?
- 90%
- Around 80% for NAP1 and more severe infection
- Recurrence = over 20-25%
What is considered a tx failure of metro for non-severe CDI?
- Lack of clinical improvement w/in 2 days
- Fever lasting 3 or more days
- GI sx lasting 5 or more days
- Worsening clinical status during therapy
Adverse effects of metro for CDI
- GI
- Metallic taste
- Disulfiram-reactions
- CNS (headache, dizziness, confusion)
- Neurotoxicity
What tx would be used for CDI if PO isn’t available and why?
Metronidazole b/c it will reach the gut but vanco won’t
When is CDI considered severe?
At least 2 of
- Over 60 y/o
- sCr > 1.5x baseline (normal = 50-100 mmol/L)
- WBC > 15,000
- Temp > 38.3 C
- Albumin < 25 g/L
Tx for severe CDI
Vanco 125 mg po/ng q6h x 10-14 (including at least 7 days beyond d/c of offending agent or other antimicrobial)
Advantages to vanco over metro
- Up to 20% more effective than metro esp for severe infection
- Fewer adverse effects
- Preferred in pregnancy and lactation
Disadvantages to vanco
- Same recurrence rate as metro
- Concerns w/ collateral resistance (ex: VRE)
What is fidaxomicin and its dosing for CDI?
- Macrocyclic bactericidal antimicrobial w/ poor po absorption
- 200 mg po q12h x 10 days
Advantage and disadvantages to fidaxomicin for CDI
- Potentially lower recurrence rate
- Non-inferior compared w/ vanco for initial episodes
- Very high cost
When is CDI considered severe-complicated?
Severe + one of:
- Ileus
- Toxic megacolon
- Abdominal distention
- Hypotension
Tx for severe-complicated CDI
- Vanco 500 mg po/ng/pr (via retention enema in 100 mL NS for 1 h) q6h x 10-14 days
- AND metro 500 mg IV q8h for 5-7 days (until no longer critically ill)
When is CDI considered recurrent?
Sx and positive C. difficile toxin w/in 8 weeks of initial episode
What likely causes recurrent CDI
- Persistent spores and/or low antitoxin antibodies
- NOT antimicrobial resistance (C. diff has low resistance to many antibiotics)
When are probiotics contraindicated?
Immunocompromised px b/c they have weakened defenses and the probiotics could cause infection
Tx for 1st recurrence of CDI if initial therapy was metro
Vanco
Tx for 1st recurrence of CDI if initial therapy was vanco
- Vanco tapered-pulsed regimen (125 mg q6h x 10-14 days, then q12h x 1 week, q24h x 1 week and q2-3d x 2-8 weeks
- Or fidaxomicin
Tx for 2nd recurrence of CDI
Vanco tapered-pulsed regimen or fidaxomicin
