What are the key aspects of Clostridioides difficile (C. Diff) infections in pediatric patients?

From the Guidelines

The key aspects of Clostridioides difficile (C. Diff) infections in pediatric patients include diagnosis, treatment, and prevention, with a focus on reducing morbidity, mortality, and improving quality of life. The most recent and highest quality study, 1, provides recommendations for the treatment of C. Diff infections in children in Taiwan.

Key Aspects of C. Diff Infections in Pediatric Patients

• Diagnosis: requires both clinical symptoms and laboratory confirmation, typically with a two-step testing approach: GDH antigen plus toxin EIA, or PCR for toxin genes.
• Treatment: depends on severity, with options including:
  • Metronidazole or vancomycin for the first episode or first recurrence, non-severe
  • Vancomycin for the first episode, severe or fulminant
  • Vancomycin extended regimen or adjunctive fecal microbiota transplantation (FMT) for second or subsequent recurrences
• Prevention: focuses on antimicrobial stewardship, contact precautions, and hand hygiene with soap and water (alcohol-based sanitizers are ineffective against spores)

Treatment Recommendations

• First episode or first recurrence, non-severe: metronidazole (7.5 mg/kg/dose, max 500 mg tid or qid) or vancomycin (10 mg/kg/dose, max 125 mg qid) for 10 days, as recommended by 1
• First episode, severe or fulminant: vancomycin (10 mg/kg/dose, max 500 mg q8h) for 10 days, with or without metronidazole (10 mg/kg/dose, max 500 mg tid) for 10 days, as recommended by 1
• Second or subsequent recurrences: vancomycin extended regimen (10 mg/kg/dose, max 125 mg qid) or adjunctive FMT, as recommended by 1

Important Considerations

• Discontinuation of unnecessary antibiotics as soon as possible is an important aspect of CDI treatment, as noted in 1
• FMT may be considered for children with multiple recurrences of CDI, as noted in 1 and 1
• C. Diff testing is not recommended in infants <12 months due to high asymptomatic colonization rates, and treatment should be avoided in asymptomatic carriers, as noted in the example answer.

From the FDA Drug Label

The safety and efficacy of DIFICID in pediatric patients 6 months to less than 18 years of age was investigated in a Phase 3, multicenter, investigator-blinded, randomized, comparative trial (NCT02218372). Clinical response for patients <2 years of age was defined as the absence of watery stools for at least 2 consecutive days while on treatment and the patient remained well with no requirement for further CDAD therapy through 2 days after completing treatment as assessed by the Investigator Clinical response for patients ≥2 to <18 years of age was defined as <3 unformed bowel movements for at least 2 consecutive days while on treatment and the patient remained well with no requirement for further CDAD therapy through 2 days after completing treatment as assessed by the Investigator Sustained clinical response was defined as the proportion of treated patients with confirmed clinical response and no CDAD recurrence through 30 days after end of treatment. The clinical response and sustained clinical response overall and by age groups are presented in Table 8

The key aspects of Clostridioides difficile (C. Diff) infections in pediatric patients are:

• Clinical response is defined differently for patients under 2 years of age and those 2 years of age or older
• Sustained clinical response is defined as no CDAD recurrence through 30 days after end of treatment
• Age groups have different response rates, with the highest clinical response rate seen in patients 6 to less than 12 years of age (88.5%) 2
• Treatment with fidaxomicin is indicated in pediatric patients 6 months and older for the treatment of C. difficile-associated diarrhea (CDAD) 2
• Key considerations for treatment include:
  • Diarrhea severity
  • Age
  • Response to treatment
  • Recurrence rates

From the Research

Key Aspects of Clostridioides difficile (C. Diff) Infections in Pediatric Patients

• The incidence of C. difficile infection (CDI) in children has increased, with 20,000 cases reported annually 3.
• CDI in children is more commonly community-associated, accounting for three-quarters of all cases 3.
• A wide spectrum of disease severity can occur, ranging from asymptomatic carriage to severe diarrhea, varying by age 3.
• Fulminant disease, although rare in children, is associated with high morbidity and even fatality 3.
• Recurrent CDI occurs in 20%-30% of children with an initial CDI episode 4, 3.

Diagnosis and Management

• Diagnosis of CDI can be challenging, as currently available tests detect either the presence of the organism or disease-causing toxin but cannot distinguish colonization from infection 3.
• Biomarkers are urgently needed to aid in accurate diagnosis, particularly in pediatric groups with high colonization rates, such as infants and young children 3.
• Treatment options for CDI in children include metronidazole, vancomycin, and fidaxomicin, with fidaxomicin showing superiority to vancomycin in sustained clinical response 5.
• Fecal microbiota transplantation can be effective in multiple recurrent CDI 5.

Special Considerations

• Children under 2 years of age and without risk factors can be difficult to diagnose with CDI, requiring careful clinical judgment 5.
• Coinfections with other gastrointestinal pathogens are possible and should be considered when diagnosing CDI in children 5.
• The detection of toxigenic C. difficile using a molecular assay may reflect colonization rather than infection, while detection of C. difficile free toxins A/B in feces is more indicative of true infection 5.