Clostridium difficile in pediatric populations Flashcards
Where is clostridium difficile found?
- Soil
- Hospital environments
- Child care facilities
- Nursing homes
What is the primary mode of transmission?
Person-to-person spread by the fecal-oral route
What are the rates of asymptomatic carriers in children?
- 15-63% neonates
- 3-33% infants and toddler <2yo
- 8.3% older children >2yo
Why do infants and young children rarely develop symptoms?
- Immature surface receptors for C. diff
2. Protection by maternal antibodies acquired transplacentally or in breast milk
What is the incubation period of C. diff from exposure to onset of symptoms?
Median 2-3 days
What are risk factors for pediatric C. difficile infection?
- Duration of hospital stay
- Older age
- Exposure to multiple antibiotic classes
- Anti-microbial use
- Chemotherapy
- Immunosuppression esp. HIV
- IBD
- Hypogammaglobulinemia
- GI surgery
- Manipulation of the GI tract including tube feeding
What is the rate of recurrent infection with C. diff?
~25%
What pathophysiologic features of C. diff make it more virulent?
- Heat resistant spores
- Acid restistant spores
- Toxin A (enterotoxin) production to disrupt neuronal function and cause aberrant release of calcium
- 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
What are the clinical features of mild C difficile?
- Watery diarrhea with fewer than four abnormal stools per day
- No systemic toxicity
What are the clinical features of moderate C. difficile?
- Four or more abnormal watery diarrheal stools per day
- No systemic toxicity
- Mild abdominal pain?
- Low grade fever?
What are the clinical features of severe C. difficile disease?
- Evidence of systemic toxicity e.g. high grade fver, rigors
- Abdominal pain
- Leukocytosis
- Progressively severe diarrhea containing blood, mucus, and leukocytes
What are some complications of severe C. difficile (aka pseudomembranous colitis)?
- Hypotension
- Shock
- Peritonitis
- Ileus
- Toxic megacolon
- Intestinal perforation
Which children are more likely to have complications with C. difficile infection?
- Neutropenic children w/ hematological malignancies
- HSCT
- Hirschprung’s disease
- IBD
What tests are available for diagnosis of C. difficile?
- Enzyme immunoassay (IA) for glutamate dehydrogenase (GDH) - (present in almost all strains of C. diff incld. strains that do not produce toxin)
- EIA for toxins A and B
- Cell cytotoxin assay - cytotoxicity of stool for human foreskin fibroblast cells
- Clostridium difficile culture (sensitivity 95%, low specificity, long turnaround time)
What are strategies to prevent C. difficile infection?
- Meticulous hand hygiene with soap and water (alcohol-based hand hygiene products do NOT kill C. diff)
- Identifying and removing environmental sources of C. difficile
- Use chlorine-containing or other sporicidal cleaning agents to eliminate environmental contamination in areas associated with increased rates of CDI outbreaks
- Use of private rooms or cohorting
- Do not retest stools once symptoms abate
- Isolate patients based on symptoms alone
- Antimicrobial stewardship initiatives
- Probiotics (insufficient evidence)
What happens to C difficile and the toxin in stool with treatment?
It does not eradicate the toxin so do not retest stools once symptoms abate.
When should C-difficile-associated colitis be considered?
- 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
- 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)
When should C difficile-associated diarrhea be diagnosed?
Only if toxin is detected in the stool. Culture of the bacteria is not sufficient evidence to support the diagnosis in symptomatic patients
Should asymptomatic patients be tested?
No, there is no clinical significance in patients without symptoms
What is the treatment for initial episode mild CDI?
- Stop antibiotics if possible
2. Return if symptoms worsen or if child does not improve within 48h
What is the treatment for initial episode moderate CDI?
Oral metronidazole (30mg/kg/day divided QID x 10-14d, max 2g/day)
What is the treatment for initial episode severe CDI?
Oral vancomycin (40mg/kg/day divided QID x 10-14d, max 500mg/day)
What is the treatment for initial episode severe complicated CDI (ileus, megacolon, shock, peritonitis, or hypotension)?
- Oral (or rectal if ileus present) vancomycin 40mg/kd/day divided QID x 10-14d, max 500mg/day) AND
- IV metronidazole (30mg/kg/day divided QID x 10-14d, max 2g/day)
What is the treatment for first recurrence CDI?
The regimen used to treat patients with first episode of C-difficile associated colitis can be repeated for the first recurrence
What is the treatment for second or later recurrences of CDI?
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
What are some second-line and experimental therapies for CDI?
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
