Department of Respiratory Sciences, NIHR Biomedical Research Centre (Respiratory theme) and Institute for Lung Health, University of Leicester, Leicester, United Kingdom.
Department of Paediatric Respiratory Medicine, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom.
Med Mycol. 2020 Jan 1;58(1):11-21. doi: 10.1093/mmy/myz015.
There is emerging evidence for the role of posaconazole in the management of Aspergillus-related cystic fibrosis (CF) lung disease. The tolerability and efficacy of posaconazole in paediatric CF is not well established. We report a prospective study over a fifty-three month period evaluating the safety, tolerability, and efficacy of posaconazole in pediatric CF. Fourteen children (seven males, median age 13 years, range 3-17 years) received a total of twenty-three courses of posaconazole (13 oral suspension and 10 tablet formulation). Of these patient episodes, nine received posaconazole for emerging or active allergic bronchopulmonary aspergillosis (ABPA) and two required a combination of posaconazole and systemic corticosteroids for difficult-to-treat ABPA. A subgroup of patients (n = 12) with persistent isolates of Aspergillus fumigatus, in the absence of serological markers of ABPA, received posaconazole monotherapy for pulmonary exacerbations not responding to conventional broad-spectrum antibiotic treatment. Posaconazole levels, full blood count, electrolytes, and liver function were monitored on day 7 of treatment and then monthly. Posaconazole was well tolerated in all but three patients. Therapeutic plasma levels >1 mg/l were achieved in all receiving the tablet formulation in comparison to 60% on the liquid preparation. There was a modest but significant improvement in FEV1 (% predicted) demonstrated for the cohort as a whole (p = 0.015) following posaconazole therapy. Posaconazole is well tolerated in children as young as six years old, improvements in lung function are observed, and therapeutic plasma levels are readily achieved in patients taking the tablet formulation and in adherent patients taking the liquid formulation.
越来越多的证据表明，泊沙康唑在治疗曲霉菌相关的囊性纤维化（CF）肺部疾病方面具有一定作用。泊沙康唑在儿科 CF 中的耐受性和疗效尚未得到充分证实。我们报告了一项前瞻性研究，该研究在 53 个月的时间内评估了泊沙康唑在儿科 CF 中的安全性、耐受性和疗效。14 名儿童（7 名男性，中位年龄 13 岁，范围 3-17 岁）共接受了 23 个疗程的泊沙康唑（13 个口服混悬液和 10 个片剂制剂）。在这些患者中，有 9 人因新发或活动性变应性支气管肺曲霉病（ABPA）接受泊沙康唑治疗，2 人因难以治疗的 ABPA 需要泊沙康唑和全身皮质类固醇联合治疗。在没有 ABPA 的血清学标志物的情况下，持续分离出烟曲霉的患者亚组（n = 12）因对常规广谱抗生素治疗无效的肺部恶化而接受泊沙康唑单药治疗。在治疗的第 7 天和之后的每月监测泊沙康唑水平、全血细胞计数、电解质和肝功能。除了 3 名患者之外，所有患者均能耐受泊沙康唑治疗。与接受液体制剂的患者相比，所有接受片剂制剂的患者均能达到治疗性血浆水平>1mg/l。整个队列的 FEV1（预计百分比）都有适度但显著的改善（p = 0.015）。泊沙康唑在 6 岁以上的儿童中耐受性良好，观察到肺功能改善，并且服用片剂制剂和坚持服用液体制剂的患者均能达到治疗性血浆水平。
