Practice Based Learning: The Clostridium Difficile Conundrum

Amanda Puro, MD

Presented by Amanda Puro, MD

Clinical Question

C. Diff infection versus colonization in infants and children:

  • When do we have to treat?
  • Why not pathogenic?
  • When to worry?

Clostridium Difficile

  • Anaerobic, Gram +, spore-forming, toxin-producing bacillus
  • Pathogenesis
    • Spores → colon where turn into vegetative form and produce toxin
    • Toxins
      • A = enterotoxin
      • B = cytotoxin
      • Hypervirulent strain BI/NAP1/027 (contains binary toxin)
  • Pathogenesis
    • Unsure mechanism but theories include:
      • Alteration of colonic microflora – usually following antibiotics
      • C. Diff ingestions and toxin production
      • Mucosal injury
      • Colonization may afford protection
      • IL-8 polymorphism – impaired immune response
      • Variant in intestinal toxin receptors
  • Epidemiology
    • Prevalence increasing
      • Adults primarily
      • Pediatrics with 1.8 fold increase 1997-2006
  • Colonization
    • Neonatal period: C. Diff colonization is common – up to 50%
      • Non-pathogenic unknown why
    • Infants and children: up to 70%
      • High levels often found in asymptomatic infants
      • Once established, colonization  lasts average of 6 months (under 2yo)
      • With shifts in toxigenic and nontoxigenic strains
  • Risk factors
    • In children younger than 3-5yo, antibiotic pretreament has little role in colonization or infection
      • Older children pcn, cephalosporin, clinda, macrolides, and fluroquinolones are most implicated
    • Immunodeficiency
    • Hirschsprung disease

Research

  • C. Diff carriage rates
    • 0-1mo = 37%
    • 1-6mo = 30%
    • 6-12mo = 14%
    • By 3yo = similar rate to nonhospitalized adults (0-3%)
  • Critical Illness rare before 12-24mo
    • Theory: neonates/infants may lack the cellular machinery to bind and process toxins
  • C. Diff acquisition
    • Neonatal (early)
    • Or between 4-6th month of life (late)
    • >6mo all infants in study (12) had acquired C. Diff
    • Unknown transmission risk  to adults
    • May relate to microbial content of gut at birth compared to ~6mo of age

Recommendations

  • Testing only children who meet clinical and age-related conditions:
    • Test infants (under 12mo) limited to those with Hirschsprung disease, or other motility disorder and other alternatives sought even when test positive
    • 2-3yo have difficult to interpret results
    • >3yo positive test is likely CDI
      • Increasing risk of infection are antibiotic use, use of PPI, bowel disease, renal insufficiency, or impaired humoral immunity

Treatment

  • Discontinue offending agent
  • Antibiotic for moderate disease
    • Metronidazole 30 mg/kg/d div QID
    • Oral Vancomycin 40mg/kg/d dif QID for severe or recurrent infection
    • Contact and hand washing precautions

References

Schutze GE, Willoughby RE; Committee on Infectious Diseases; American Academy of Pediatrics. Clostridium difficile infection in infants and children. Pediatrics. 2013 Jan;131(1):196-200.

Rousseau C, Poilane I, De Pontual L, Maherault AC, Le Monnier A, Collignon A. Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. Clin Infect Dis. 2012 Nov;55(9):1209-15.

Rousseau C, Levenez F, Fouqueray C, Doré J, Collignon A, Lepage P. Clostridium difficile colonization in early infancy is accompanied by changes in intestinal microbiota composition. J Clin Microbiol. 2011 Mar;49(3):858-65.

Tamma PD, Sandora TJ. Clostridium difficile Infection in Children: Current State and Unanswered Questions. J Pediatric Infect Dis Soc. 2012 Sep;1(3):230-243.

UpToDate entry.

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