In Reply: Epidemiology and Risk Factors of Pediatric Clostridioides difficile Infection

To the Editors: We read with great interest the recent article by Yamasaki et al, entitled “Epidemiology and Risk Factors of Pediatric Clostridioides difficile Infection,” published in the September 2025 issue of this journal.1 The authors’ findings, that is, the incidence of C. difficile infection (CDI) in infants aged 0–2 years was comparable to that in older children, are valuable; however, they merit some cautious interpretation. First, the high rate of asymptomatic carriage poses a major challenge in diagnosing CDI in infants and young children, making it difficult to distinguish true infections from mere carriage. A study of Japanese children reported a C. difficile carriage rate of 37.7% in children <2 years of age without underlying diseases and 48.5% in children aged 12–23 months without underlying diseases. Furthermore, the toxin-positivity of C. difficile was 41.9% in children without underlying conditions and 75.0% in those with underlying conditions.2 This high colonization rate curtails the clinical significance of the positive test results. Second, the authors’ definition of “infection,” based on C. difficile diagnostic testing and a prescription for anti-CDI medication within 7 days, is likely an effective way to exclude asymptomatic carriage. However, the clinical benefit of treating C. difficile toxin-positive children <2 years of age remains unclear. A case-control study found no significant differences in clinical symptoms or risk factors with or without toxin-producing C. difficile in the stool. Crucially, all patients recovered regardless of metronidazole treatment.3 Thus, such treatment may cause unnecessary antimicrobial exposure. Third, diagnostic stewardship can safely reduce excessive testing and subsequent treatment for CDI in children <2 years of age.4,5 Studies that implemented strict testing restrictions or suppressed positive results reported no increase in serious adverse events, supporting guideline-based recommendations for routine testing in this age group. Although the authors included children <2 years of age in their analysis, revealing the current practice of overtesting and treatment, we recommend excluding children <2 years from the analysis to clarify the clinical characteristics of pediatric CDI and comparison with adults. In conclusion, this study provides valuable information on the current pediatric CDI testing and treatment strategies in Japan, and highlights the potential for overdiagnosis and overtreatment in children <2 years of age. Furthermore, the study underscores the need to raise awareness about diagnostic stewardship among Japanese pediatricians. We thank the authors for their contributions to this important field and hope that our comments will encourage further research toward establishing diagnostic management in this age group.