2 - Clostridium Difficile Infection

Question 1

What is clostridium difficile?

Answer 1

• Anaerobic
• Spore forming
• Exotoxin-producing
• Gram pos bacteria

Question 2

How is C. diff transmitted?

Answer 2

Fecal-oral route

Question 3

What causes the sx of CDI?

Answer 3

Enterotoxin A and cytotoxin B

Question 4

NAP1 is associated w/ _______

Answer 4

Fluoroquinolone use

Question 5

What is the significance of NAP1 C. diff strain?

Answer 5

• 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

Question 6

Over ___% of CDI associated w/ NAP1

Answer 6

30%

Question 7

What are the risk factors for CDI?

Answer 7

• 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

Question 8

Which antibiotics are associated w/ CDI?

Answer 8

• Highest risk = clindamycin
• High risk = fluoroquinolones (NAP1), cephalosporins, penicillins
• Moderate risk = macrolides, sulfonamides
• Low risk = tetracyclines, aminoglycosides

Question 9

Clinical signs of CDI

Answer 9

• Watery diarrhea w/ 3 or more unformed stools in 24 h

- N/V, abdominal pain, high fever, significant leukocytosis

Question 10

Normal WBC levels

Answer 10

4.5-11 * 10^9 cells/L or 4,500-11,000 cells/uL

Question 11

Normal neutrophils levels. When do they increase?

Answer 11

• 1.8-5.2

- Increase significantly during bacterial infections

Question 12

Normal lymphocyte levels. When do they increase?

Answer 12

• 1.3-3.2

- Increase during viral infections

Question 13

Normal monocyte levels

Answer 13

0.3-0.8

Question 14

When do eosinophil levels increase?

Answer 14

Parasite infection or allergies

Question 15

Complications of CDI

Answer 15

• Most common = recurrence
• Septic shock
• Pseudomembranous or fulminant colitis
• Ileus
• Toxic megacolon (gut is immobile and expands)
• Perforation

Question 16

How is CDI diagnosed?

Answer 16

• GI sx w/ diarrhea and positive C. difficile toxin in stool

- Stool culture and molecular typing during outbreaks

Question 17

What is the sensitivity and specificity of the C. difficile assay?

Answer 17

• Sensitivity = 75-80%

- Specificity is very high, so false positives are very rare

Question 18

Strategies for preventing CDI

Answer 18

• Infection control
• Antimicrobial stewardship for clindamycin, fluoroquinolones, and other high-risk agents
• Probiotics

Question 19

What can be done to prevent the spread of CDI?

Answer 19

• 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

Question 20

General approach to treating CDI

Answer 20

• 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

Question 21

Tx for non-severe CDI

Answer 21

• 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

Question 22

What is the response and recurrence rate to metro for non-severe CDI?

Answer 22

• 90%
• Around 80% for NAP1 and more severe infection
• Recurrence = over 20-25%

Question 23

What is considered a tx failure of metro for non-severe CDI?

Answer 23

• 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

Question 24

Adverse effects of metro for CDI

Answer 24

• GI
• Metallic taste
• Disulfiram-reactions
• CNS (headache, dizziness, confusion)
• Neurotoxicity

Question 25

What tx would be used for CDI if PO isn't available and why?

Answer 25

Metronidazole b/c it will reach the gut but vanco won't

Question 26

When is CDI considered severe?

Answer 26

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

Question 27

Tx for severe CDI

Answer 27

Vanco 125 mg po/ng q6h x 10-14 (including at least 7 days beyond d/c of offending agent or other antimicrobial)

Question 28

Advantages to vanco over metro

Answer 28

- Up to 20% more effective than metro esp for severe infection - Fewer adverse effects - Preferred in pregnancy and lactation

Question 29

Disadvantages to vanco

Answer 29

- Same recurrence rate as metro | - Concerns w/ collateral resistance (ex: VRE)

Question 30

What is fidaxomicin and its dosing for CDI?

Answer 30

- Macrocyclic bactericidal antimicrobial w/ poor po absorption - 200 mg po q12h x 10 days

Question 31

Advantage and disadvantages to fidaxomicin for CDI

Answer 31

- Potentially lower recurrence rate - Non-inferior compared w/ vanco for initial episodes - Very high cost

Question 32

When is CDI considered severe-complicated?

Answer 32

Severe + one of: - Ileus - Toxic megacolon - Abdominal distention - Hypotension

Question 33

Tx for severe-complicated CDI

Answer 33

- 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)

Question 34

When is CDI considered recurrent?

Answer 34

Sx and positive C. difficile toxin w/in 8 weeks of initial episode

Question 35

What likely causes recurrent CDI

Answer 35

- Persistent spores and/or low antitoxin antibodies | - NOT antimicrobial resistance (C. diff has low resistance to many antibiotics)

Question 36

When are probiotics contraindicated?

Answer 36

Immunocompromised px b/c they have weakened defenses and the probiotics could cause infection

Question 37

Tx for 1st recurrence of CDI if initial therapy was metro

Answer 37

Vanco

Question 38

Tx for 1st recurrence of CDI if initial therapy was vanco

Answer 38

- 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

Question 39

Tx for 2nd recurrence of CDI

Answer 39

Vanco tapered-pulsed regimen or fidaxomicin