The US Food and Drug Administration (FDA) has approved a new drug application (NDA) for the macrolide antibacterial fidaxomicin (Dificid, Merck) for oral suspension, and a supplemental NDA for fidaxomicin tablets for treatment of Clostridioides difficile-associated diarrhea (CDAD) in children aged 6 months and older.

C difficile is one of the most common causes of healthcare-associated infections in US hospitals, causing nearly 500,000 infections annually and roughly 29,000 deaths within 30 days of initial diagnosis.

In the 2019 Antibiotic Resistance Threats Report, federal health officials label C difficile an urgent public health threat requiring urgent and aggressive action, as reported by Medscape Medical News. 

"The fidaxomicin pediatric trial was the first randomized controlled trial of C difficile infection treatment in children," Larry K. Kociolek, MD, associate medical director of infection prevention and control at Ann & Robert H. Lurie Children's Hospital of Chicago, said in a company news release. "I am very excited to have a new C difficile infection treatment option for my pediatric patients."

The FDA approved the new formulation and new indication for fidaxomicin based on the phase 3 SUNSHINE study, which demonstrated the safety and efficacy of fidaxomicin in pediatric patients aged 6 months to younger than 18 years. The study included 148 patients with confirmed C difficile infection, of whom 142 received either fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, four times daily).

The clinical response against CDAD in the overall pediatric population, assessed through 2 days after 10 days of treatment, was similar between the fidaxomicin and vancomycin groups (77.6% vs 70.5%), according to Merck.

Sustained clinical response, defined as the proportion of treated patients with confirmed clinical response and no CDAD recurrence through 30 days after the end of treatment, was higher for fidaxomicin than for vancomycin (68.4% vs 50%).

The safety of fidaxomicin in children was evaluated in a phase 2 single-group trial and a phase 3 randomized, active-controlled trial. Treatment discontinuation as a result of adverse reactions occurred in 3 (7.9%) of 38 patients in the phase 2 trial, and in 1 (1%) of 98 and 1 (2.3%) of 44 patients treated with fidaxomicin and vancomycin, respectively, in the phase 3 trial.

The most common adverse reactions seen in patients treated with fidaxomicin in the phase 3 trial were pyrexia (13.3%), abdominal pain (8.2%), vomiting (7.1%), diarrhea (7.1%), constipation (5.1%), increased aminotransferases (5.1%), and rash (5.1%).

One death occurred in the phase 2 single-group trial and three deaths occurred in the phase 3 trial of fidaxomicin-treated patients. No deaths occurred in vancomycin-treated patients during the study period (40 days). All deaths occurred in patients younger than 2 years and appeared to be related to underlying comorbidities.

To curb development of drug-resistant bacteria, fidaxomicin should be used only to treat infections that are proven or strongly suspected to be caused by C difficile, Merck said. Fidaxomicin should not be used in patients with known hypersensitivity to the drug or any other ingredient in Dificid.