Safety and Efficacy of Anidulafungin in the Treatment of Invasive Candidiasis in Children

Abstract

Background Treatment with an echinocandin is recommended as first-line therapy of patients with invasive candidiasis including candidemia (ICC). Little is known about the efficacy and safety of anidulafungin (ANID) for the management of ICC in children.Methods Subjects aged 1 months to 17 years with ICC were enrolled into a prospective, open-label, non-comparative, multi-center, global study (NCT00761267) to receive ANID (3 mg/kg on day 1, 1.5 mg/kg daily thereafter). An interim analysis was completed in children 2–17 years. Subjects were to receive ANID for at least 10 days up to 35 days. A central venous catheter suspected as a site of infection was to be removed. A switch to oral fluconazole could be made after day 10. Treatment was required for at least 14 days after two negative cultures separated by 24 hours. Efficacy, based on a determination of global response (combination of clinical and microbiological response), was assessed at end of IV treatment (EOIVT), end of treatment (EOT), 2- and 6-week follow-up. Safety was assessed through 6-week follow-up.ResultsIn total, 48 subjects (18, 2 to <5 years; 30, 5–17 years) received at least 1 dose of ANID (mean 11 days; range 1–35 days) and were assessed for safety. Forty-seven subjects had microbiologically confirmed ICC and were evaluated for efficacy. The most common baseline pathogens were C. albicans (38%) and C. parapsilosis (26%). Forty-four (93.6%) subjects had candidemia only. Global response success rates at EOIVT and EOT were 72.3 and 74.5%, respectively. All subjects reported at least one treatment emergent adverse event (AE) with diarrhea (22.9%), vomiting (22.9%), and pyrexia (18.8%) being most frequent. Five subjects discontinued treatment due to AEs of which four [increased transaminases (2), vomiting, pruritus generalis] were considered related to ANID. All-cause mortality by the 2- and 6-week follow-up visit was 12.5 and 14.6%, respectively. Of the seven deaths during the study, one was considered related to ICC; two were related to disease progression (Ewing’s sarcoma, medulloblastoma); the remaining were related to other conditions (intracranial hemorrhage, sepsis/septic shock, and respiratory failure).Conclusion Anidulafungin was effective with an acceptable tolerability and safety profile in children aged 2–17 years diagnosed with ICC.Disclosures E. Roilides, Pfizer: Grant Investigator, Investigator, Research Contractor and Speaker’s Bureau, Grant recipient, Research grant and Speaker honorarium. H. Leister-Tebbe, Pfizer: Employee, Salary. U. Conte, Pfizer Inc.: Employee, Salary. J. L. Yan, Pfizer: Employee, Salary. P. Liu, Pfizer: Employee, Salary. M. Tawadrous, Pfizer: Employee, Salary. J. Aram, Pfizer Inc.: Employee, Salary. F. Queiroz-Telles, Pfizer: Grant Investigator, Research grant