Fidaxomicin Treatment of <i>Clostridioides difficile</i> Infections

Source: Conrad MA, Kaplan AL, Weinbrom S, et al. Fidaxomicin treatment of Clostridioides difficile infections and recurrences in children and adolescents: a retrospective multicenter study. J Pediatr. 2025;285:114681; doi: 10.1016/j.jpeds.2025.114681.Investigators from multiple institutions conducted a retrospective study to evaluate the effectiveness of fidaxomicin for treatment of Clostridioides difficile infection (CDI) in children. Study participants were patients 12 months to 18 years old with primary or recurrent CDI treated with fidaxomicin at 5 centers in the US between 2013 and 2021. The medical records of these children were reviewed and demographic and clinical data extracted. The diagnosis of CDI was based on the presence of ≥3 watery stools in 24 hours and a positive toxin enzyme immunoassay or PCR. Outcomes were assessed at 14 and 60 days after initiation of fidaxomicin. At day 14, patients were classified as having a clinical cure if there was complete resolution of diarrhea and other signs of CDI, improved if symptoms were less severe but not resolved, or as a treatment failure. Children with an initial response (clinical cure or improved) were followed for up to 60 days to assess recurrence of CDI, defined as worsening or return of symptoms and a repeat positive test for CDI. As a secondary analysis, the proportion of study children with inflammatory bowel disease (IBD) with an initial response to fidaxomicin was compared to that of those without IBD. For those with an initial response, the rate of relapse in patients with and without IBD were compared.Data were analyzed on 95 children with CDI, including 11 (11.7%) with an initial episode of CDI and 83 (87.4%) with recurrent CDI. The median age of study patients was 12 years; 86.3% had a comorbidity, including 29 (30.5%) with IBD and 27 (28.4%) with a feeding tube. The duration of fidaxomicin treatment was 10 days in 84 study participants, 14 days in 8, and 17–30 days in 3. At day 14 after initiation of treatment, 50 (52.6%) patients had a clinical cure and 29 (30.5%) were improved. Of the 79 children with a clinical cure or improvement in symptoms following fidaxomicin treatment, 17 (21.5%) had a recurrence by day 60. The median time to recurrence in these patients was 31 days. Patients with IBD were significantly less likely than those without IBD to have a clinical cure 14 days after initiation of fidaxomicin treatment (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.11, 0.70). However, in the 20 children with IBD and CDI who had an initial response to fidaxomicin, the risk of a recurrence by day 60 was not significantly increased (OR, 1.31; 95% CI, 0.40, 4.31).The authors conclude that fidaxomicin treatment for children with CDI was associated with low rates of treatment failure.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.About 20,000 US children develop CDI each year.1 The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) published clinical practice guidelines for the diagnosis and management of CDI in children in 2017.2 The management of CDI in children is determined by the age of the child, severity, and number of episodes.3 Young children may be colonized with C. difficile, but symptomatic disease is rare. For symptomatic children, discontinuation of any inciting antibiotic, when feasible, is a first step to limit further intestinal microbial disruption.3 The 2017 guidelines recommended either oral metronidazole or oral vancomycin for the treatment of a first episode of non-severe CDI in a child.2 When the guidelines were updated for adults in 2021, oral metronidazole was removed as a first-line therapy, and fidaxomicin was preferred over oral vancomycin because CDI recurrences were fewer following fidaxomicin compared to vancomycin.4The SUNSHINE study enrolled and randomized 142 children with non-severe CDI to receive either oral vancomycin or fidaxomicin.5 The rate of response at day 30 after therapy was higher with fidaxomicin compared with vancomycin. Based on these results, the US Food and Drug Administration expanded approval of fidaxomicin for treatment of CDI to include children 6 months and older.6 Children with CDI, especially those with severe or recurrent disease, now often are treated with either oral vancomycin or fidaxomicin.3 The current study included children with IBD who were excluded from the SUNSHINE study, and treatment decisions were at the discretion of the child’s physician. Fidaxomicin was well-tolerated, with low rates of treatment failure. However, there was no comparison group with oral vancomycin. Additional studies are needed to guide clinicians in choosing among the available therapies for CDI in children.Fidaxomicin therapy for children with CDI is associated with a good clinical response.Although health care-associated CDI infections are decreasing in children as well as in adults, community-associated pediatric CDI appear to be increasing.7 Contributing factors include comorbidities and increased antibiotic use—yet another reason for antimicrobial stewardship.