Division of Anti-Infectives, Office of Infectious Diseases, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA.
Division of Infectious Disease Pharmacology, Office of Clinical Pharmacology, Office of Translational Sciences, Food and Drug Administration, Silver Spring, Maryland, USA.
Clin Infect Dis. 2021 Dec 16;73(12):2335-2340. doi: 10.1093/cid/ciab025.
Pathogenesis of neonatal candidiasis (NC) is distinct from systemic candidiasis in adults and older pediatric patients due to the significant incidence of central nervous system involvement in neonates. Thus, although adequate and well-controlled trials in NC are often unfeasible due to difficulty enrolling patients, extrapolation of efficacy from antifungal drug trials in adults is generally not appropriate. However, treatment of NC is an area of great unmet need. We describe a regulatory review approach that combined the assessment of limited clinical efficacy, pharmacokinetics, and safety data from neonates and young infants along with microbiology outcomes and pharmacokinetic data from relevant nonclinical models of candidemia/invasive candidiasis to inform the use of micafungin in pediatric patients younger than 4 months, while communicating areas of remaining uncertainty in labeling.
新生儿念珠菌病(NC)的发病机制与成人和大龄儿科患者的系统性念珠菌病不同,因为中枢神经系统在新生儿中的受累发生率很高。因此,尽管由于难以招募患者,针对 NC 的充分和良好对照试验往往不可行,但从成人抗真菌药物试验中推断疗效通常是不合适的。然而,NC 的治疗是一个巨大的未满足需求领域。我们描述了一种监管审查方法,该方法结合了对新生儿和婴儿有限的临床疗效、药代动力学和安全性数据的评估,以及来自相关念珠菌血症/侵袭性念珠菌病非临床模型的微生物学结果和药代动力学数据,以告知在 4 个月以下儿科患者中使用米卡芬净,同时在标签中说明仍存在不确定性的领域。