Clostridium difficile in pediatric populations

Question 1

Where is clostridium difficile found?

Answer 1

1. Soil
2. Hospital environments
3. Child care facilities
4. Nursing homes

Question 2

What is the primary mode of transmission?

Answer 2

Person-to-person spread by the fecal-oral route

Question 3

What are the rates of asymptomatic carriers in children?

Answer 3

1. 15-63% neonates
2. 3-33% infants and toddler <2yo
3. 8.3% older children >2yo

Question 4

Why do infants and young children rarely develop symptoms?

Answer 4

1. Immature surface receptors for C. diff

2. Protection by maternal antibodies acquired transplacentally or in breast milk

Question 5

What is the incubation period of C. diff from exposure to onset of symptoms?

Answer 5

Median 2-3 days

Question 6

What are risk factors for pediatric C. difficile infection?

Answer 6

1. Duration of hospital stay
2. Older age
3. Exposure to multiple antibiotic classes
4. Anti-microbial use
5. Chemotherapy
6. Immunosuppression esp. HIV
7. IBD
8. Hypogammaglobulinemia
9. GI surgery
10. Manipulation of the GI tract including tube feeding

Question 7

What is the rate of recurrent infection with C. diff?

Answer 7

~25%

Question 8

What pathophysiologic features of C. diff make it more virulent?

Answer 8

1. Heat resistant spores
2. Acid restistant spores
3. Toxin A (enterotoxin) production to disrupt neuronal function and cause aberrant release of calcium
4. Toxin B (cytotoxin) production altering chemotaxis of neutrophils, activation of macrophages and mast cells, and induction of inflammatory mediator release
   Toxin production –> fluid secretion, mucosal damage, interstitial inflammation

Question 9

What are the clinical features of mild C difficile?

Answer 9

1. Watery diarrhea with fewer than four abnormal stools per day
2. No systemic toxicity

Question 10

What are the clinical features of moderate C. difficile?

Answer 10

1. Four or more abnormal watery diarrheal stools per day
2. No systemic toxicity
3. Mild abdominal pain?
4. Low grade fever?

Question 11

What are the clinical features of severe C. difficile disease?

Answer 11

1. Evidence of systemic toxicity e.g. high grade fver, rigors
2. Abdominal pain
3. Leukocytosis
4. Progressively severe diarrhea containing blood, mucus, and leukocytes

Question 12

What are some complications of severe C. difficile (aka pseudomembranous colitis)?

Answer 12

1. Hypotension
2. Shock
3. Peritonitis
4. Ileus
5. Toxic megacolon
6. Intestinal perforation

Question 13

Which children are more likely to have complications with C. difficile infection?

Answer 13

1. Neutropenic children w/ hematological malignancies
2. HSCT
3. Hirschprung’s disease
4. IBD

Question 14

What tests are available for diagnosis of C. difficile?

Answer 14

1. Enzyme immunoassay (IA) for glutamate dehydrogenase (GDH) - (present in almost all strains of C. diff incld. strains that do not produce toxin)
2. EIA for toxins A and B
3. Cell cytotoxin assay - cytotoxicity of stool for human foreskin fibroblast cells
4. Clostridium difficile culture (sensitivity 95%, low specificity, long turnaround time)

Question 15

What are strategies to prevent C. difficile infection?

Answer 15

1. Meticulous hand hygiene with soap and water (alcohol-based hand hygiene products do NOT kill C. diff)
2. Identifying and removing environmental sources of C. difficile
3. Use chlorine-containing or other sporicidal cleaning agents to eliminate environmental contamination in areas associated with increased rates of CDI outbreaks
4. Use of private rooms or cohorting
5. Do not retest stools once symptoms abate
6. Isolate patients based on symptoms alone
7. Antimicrobial stewardship initiatives
8. Probiotics (insufficient evidence)

Question 16

What happens to C difficile and the toxin in stool with treatment?

Answer 16

It does not eradicate the toxin so do not retest stools once symptoms abate.

Question 17

When should C-difficile-associated colitis be considered?

Answer 17

1. Any patient who receives or has received antibiotics within the previous 12 weeks and has the following signs: bloody diarrhea with or without systemic toxicity, fever, and abdominal pain
2. Any immunocompromised patient who are receiving or have received antibiotics or chemotherapy within the previous 12 weeks and have any diarrheal illness (either watery or bloody)

Question 18

When should C difficile-associated diarrhea be diagnosed?

Answer 18

Only if toxin is detected in the stool. Culture of the bacteria is not sufficient evidence to support the diagnosis in symptomatic patients

Question 19

Should asymptomatic patients be tested?

Answer 19

No, there is no clinical significance in patients without symptoms

Question 20

What is the treatment for initial episode mild CDI?

Answer 20

1. Stop antibiotics if possible

2. Return if symptoms worsen or if child does not improve within 48h

Question 21

What is the treatment for initial episode moderate CDI?

Answer 21

Oral metronidazole (30mg/kg/day divided QID x 10-14d, max 2g/day)

Question 22

What is the treatment for initial episode severe CDI?

Answer 22

Oral vancomycin (40mg/kg/day divided QID x 10-14d, max 500mg/day)

Question 23

What is the treatment for initial episode severe complicated CDI (ileus, megacolon, shock, peritonitis, or hypotension)?

Answer 23

1. Oral (or rectal if ileus present) vancomycin 40mg/kd/day divided QID x 10-14d, max 500mg/day) AND
2. IV metronidazole (30mg/kg/day divided QID x 10-14d, max 2g/day)

Question 24

What is the treatment for first recurrence CDI?

Answer 24

The regimen used to treat patients with first episode of C-difficile associated colitis can be repeated for the first recurrence

Question 25

What is the treatment for second or later recurrences of CDI?

Answer 25

Oral vancomycin with tapering and/or pulsed regimen:

• 10mg/kg/dose QID x 10-14d
• 10mg/kg/dose BID x 1wk
• 10mg/kg/dose daily x 1wk
• 10mg/kg/dose q2-3d x 2-8wk

Question 26

What are some second-line and experimental therapies for CDI?

Answer 26

Consider other therapies on a case-by-case basis in consultation w/ an ID specialist.

• Rifaximin
• Rifampin?
• Saccharomyces boulardii and other probiotics
• Teicoplanin
• Fidaxomicin
• Nitazoxanide
• Tinidazole
• IV immunoglobulin
• fecal transplants