Fidaxomicin shines in paediatric C. difficile infection

Treatment with fidaxomicin in children and teens with Clostridium difficile infection (CDI) is safe and well tolerated and frequently leads to cure compared with vancomycin, according to the results of the phase III SUNSHINE trial.

“Our safety results are particularly favourable given the young patient population enrolled, the higher percentage of patients with prior CDI in the fidaxomicin arm, and the large proportion of patients with co-infections and haematological malignancies,” the investigators said.

The safety and efficacy analyses included 142 CDI patients (40.54 percent female) aged <18 years who were randomly assigned to 10 days of treatment with either fidaxomicin (suspension or tablets, twice daily; n=98; median age, 60.0 months) or vancomycin (suspension or tablets, four times daily; n=44; median age, 48.0 months). All patients were followed until 30 days after treatment.

Treatment-emergent adverse events (TEAEs) occurred with similar frequency in the fidaxomicin and vancomycin arms (73.5 percent vs 75.0 percent). There were two TEAEs that resulted in treatment withdrawal: a case of moderate colitis in the former arm and severe vomiting in the latter. Three patients died in the fidaxomicin arm during the study period and two in the vancomycin arm shortly after the end of the study. [Clin Infect Dis 2019;doi:10.1093/cid/ciz1149]

The rate of confirmed clinical response (CCR) at 2 days after end of treatment did not significantly differ between the two treatment arms: 77.6 percent with fidaxomicin and 70.5 percent with vancomycin (adjusted treatment difference, 7.5 percent, 95 percent confidence interval [CI], –7.4 to 23.9).

Meanwhile, fidaxomicin yielded a markedly higher rate of global cure, defined as CCR without CDI recurrence (68.4 percent vs 50.0 percent; adjusted treatment difference, 18.8 percent, 95 percent CI, 1.5–35.3). Accordingly, the cumulative incidence of recurrence was significantly higher with vancomycin (log-rank, p=0.023).

“[D]ue to a numerically higher CCR and a lower rate of recurrence, fidaxomicin-treated patients had a significantly higher rate of global cure. The number needed to treat to prevent one additional treatment failure or recurrence was 5.3 (95 percent CI, 2.8–66.7),” the investigators pointed out.

They added: “The subgroup of immunocompromised patients also showed improved clinical outcomes with fidaxomicin than vancomycin, although treatment differences were not significant; this result is encouraging as this patient population is at particularly high risk of CDI incidence and recurrence. The apparently lower treatment effect in this population, compared with the overall FAS, may reflect a greater likelihood for these patients to have an alternative or a multifactorial aetiology for diarrhoea, and/or to require additional antibiotics during treatment or follow up.”

In terms of pharmacokinetics, systemic absorption of fidaxomicin and its metabolite OP-1118 was minimal and stool concentrations were high.

Said to be the first to assess the safety and efficacy of the narrow-spectrum antibiotic fidaxomicin in paediatric CDI, the study had several limitations including the single-blinded design and the limited recruitment numbers due to the specific population targeted.