Clostridioides difficile Infection in Children: Recent Updates on Epidemiology, Diagnosis, Therapy

Abstract

Clostridioides (formerly Clostridium) difficile is the most important infectious cause of antibiotic-associated diarrhea worldwide and a leading cause of healthcare-associated infection in the United States. The incidence of C. difficile infection (CDI) in children has increased, with 20 000 cases now reported annually, also posing indirect educational and economic consequences. In contrast to infection in adults, CDI in children is more commonly community-associated, accounting for three-quarters of all cases. A wide spectrum of disease severity ranging from asymptomatic carriage to severe diarrhea can occur, varying by age. Fulminant disease, although rare in children, is associated with high morbidity and even fatality. Diagnosis of CDI can be challenging as currently available tests detect either the presence of organism or disease-causing toxin but cannot distinguish colonization from infection. Since colonization can be high in specific pediatric groups, such as infants and young children, biomarkers to aid in accurate diagnosis are urgently needed. Similar to disease in adults, recurrence of CDI in children is common, affecting 20% to 30% of incident cases. Metronidazole has long been considered the mainstay therapy for CDI in children. However, new evidence supports the safety and efficacy of oral vancomycin and fidaxomicin as additional treatment options, whereas fecal microbiota transplantation is gaining popularity for recurrent infection. Recent advancements in our understanding of emerging epidemiologic trends and management of CDI unique to children are highlighted in this review. Despite encouraging therapeutic advancements, there remains a pressing need to optimize CDI therapy in children, particularly as it pertains to severe and recurrent disease.

FIGURE 1

The impact of Clostridioides difficile infection in children.

FIGURE 2

Severe Clostridioides difficile infection in children. (A) Abdominal radiograph showing thickened colon most prominent in the transverse colon. (B) Abdominal sonogram showing hypoechoic diffuse large bowel wall thickening. (C) CT Abdomen and pelvis showing markedly thickened colon wall in an adolescent with fulminant C. difficile colitis.

FIGURE 3

A laboratory testing approach for diagnosis of Clostridioides difficile infection in children.^{a a}Based on the 2017 IDSA and SHEA guideline, which recommends a 2-step algorithm, including s stool toxin test (ie, glutamate dehydrogenase EIA plus Toxin EIA, arbitrated by NAAT or NAAT plus toxin EIA) as the best diagnostic approach. Discordant results require further clinical evaluation. c/w, consistent with; CDI, Clostridioides difficile infection; EIA, enzyme immunoassay; GDH, glutamate dehydrogenase; ID, Infectious Disease; NAAT, nucleic acid amplification test; Toxin A/B, Toxin A and B enzyme immunoassay; yo, years old.