Two-step Testing for Clostridioides Difficile is Inadequate in Differentiating Infection From Colonization in...

Area of Science:

• Pediatric Infectious Diseases
• Clinical Microbiology
• Diagnostic Test Evaluation

Background:

• Recent guidelines recommend multistep testing algorithms for Clostridioides difficile infection (CDI) diagnosis.
• These algorithms combine nucleic acid amplification-based testing (NAAT) and toxin enzyme immunoassay (EIA).
• The utility of these algorithms in children, particularly in differentiating colonization from active infection, remains unevaluated.

Purpose of the Study:

• To evaluate the effectiveness of multistep testing algorithms in diagnosing CDI in pediatric patients.
• To assess the ability of NAAT and EIA combined to differentiate between C. difficile colonization and CDI in children.
• To investigate the performance of a cell cytotoxicity neutralization assay (CCNA) in pediatric CDI diagnosis.

Main Methods:

• Prospective enrollment of asymptomatic pediatric patients with cancer, cystic fibrosis (CF), or inflammatory bowel disease (IBD).
• Stool samples were tested using NAAT; positive samples underwent EIA.
• Symptomatic children with CDI were also enrolled, with EIA and CCNA performed on stool samples.

Main Results:

• Of 225 asymptomatic children, 47 (21%) were colonized with C. difficile.
• 41 symptomatic children with CDI were enrolled.
• Neither EIA nor CCNA positivity significantly differed between colonized and symptomatic children, nor predicted disease severity.

Conclusions:

• Multistep testing algorithms (NAAT followed by EIA) failed to differentiate symptomatic CDI from asymptomatic colonization in pediatric patients.
• Pediatric providers must be aware of the limitations of these diagnostic algorithms when used in children.
• Further research may be needed to refine diagnostic strategies for CDI in pediatric populations.