Clostridioides difficile (C. difficile) is the leading cause of infection among patients on antibiotic therapy, with disease severity (CDI) varying by age and patient charac-teristics, ranging from asymptomatic to severe cases such as diarrhoea and septic shock. CDI is seldom observed in newborns due to the immaturity of their intestinal mucosa, which lacks receptors for toxins. Even with its low incidence in this population, clinicians must remain vigilant for its diagnosis when risk factors are present. The article reviews epidemiological data, diagnostic methods and case reports, including a severe CDI case in a new-born with Down syndrome who developed septic shock after antibiotic therapy. The analysis emphasises the importance of suspecting C. difficile infection in patients with severe diarrhoea, particularly those with risk factors like congenital malformations and prolonged antibiotic use. Furthermore, the paper outlines an appropriate diagnostic approach, recommending ELISA immunoassays for detecting glutamate dehydrogenase and toxins, followed by confirmatory tests if needed. Oral vancomycin is the preferred treatment, with additional supportive measures recommended for severe cases.