Department of Pharmacy, Children's Hospital Colorado, Aurora, CO.
J Pediatr Hematol Oncol. 2024 Aug 1;46(6):e419-e425. doi: 10.1097/MPH.0000000000002898. Epub 2024 Jun 21.
Invasive fungal infections are a significant cause of morbidity and mortality in children with immunodeficiencies. Current dosing recommendations for voriconazole often result in subtherapeutic exposure in pediatric patients. In this single-center retrospective study, we reviewed hospitalized pediatric patients receiving voriconazole with at least one inpatient serum trough concentration measured. Patient characteristics and voriconazole dosing courses with associated trough concentrations were summarized for all patients as well as grouped by age (0 to 1 y, 2 to 11 y, and 12 to 18 y). Of 106 included patients, the median age was 9 years (range, 29 d to 18 y). Five hundred ninety courses of voriconazole were administered with 365 associated troughs. Most troughs were subtherapeutic (49%) and 30% of patients never attained a therapeutic trough. The median oral daily dose associated with a therapeutic trough was higher in younger age groups: 21.6 mg/kg 0 to 1 year, 17.9 mg/kg 2 to 11, and 9.5 mg/kg 12 to 18 years ( P <0.001). Patients younger than 2 years had the largest proportion of subtherapeutic troughs and variability in dosing. Attainment of therapeutic voriconazole concentrations was challenging across all pediatric age groups. Higher starting doses for patients younger than 2 years are likely needed.
侵袭性真菌感染是免疫缺陷儿童发病率和死亡率的重要原因。目前伏立康唑的推荐剂量常导致儿科患者的药物暴露不足。在这项单中心回顾性研究中,我们对接受伏立康唑治疗且至少有一次住院患者谷浓度检测值的住院儿科患者进行了回顾。我们对所有患者的患者特征和伏立康唑剂量方案及其相关谷浓度进行了总结,并按年龄(0 至 1 岁、2 至 11 岁和 12 至 18 岁)进行了分组。在 106 例纳入患者中,中位年龄为 9 岁(范围为 29 天至 18 岁)。共给予 590 个伏立康唑疗程,其中 365 个疗程有相关谷浓度。大多数谷浓度低于治疗范围(49%),30%的患者从未达到治疗性谷浓度。与治疗性谷浓度相关的中位口服日剂量在年龄较小的组中更高:0 至 1 岁组为 21.6mg/kg,2 至 11 岁组为 17.9mg/kg,12 至 18 岁组为 9.5mg/kg(P<0.001)。年龄小于 2 岁的患者谷浓度低于治疗范围的比例和剂量变化最大。所有儿科年龄组均难以达到治疗性伏立康唑浓度。年龄小于 2 岁的患者可能需要更高的起始剂量。