Martin Judith M, Macias-Parra Mercedes, Mudry Peter, Conte Umberto, Yan Jean L, Liu Ping, Capparella M Rita, Aram Jalal A
From the *Division of General Academic Pediatrics, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania; †Pediatric Infectious Diseases Department, Instituto Nacional de Pediatria, Mexico City, Mexico; ‡Department of Pediatric Oncology, University Children's Hospital Brno, Brno, Czech Republic; §Antifungal Clinical Development, Pfizer Inc., New York, New York; ¶Global Established Pharma-Biostatistics, Pfizer Inc., New York, New York; ‖Department of Clinical Pharmacology, Pfizer Inc., Groton, Connecticut; **Global Established Pharma, Pfizer PFE, Paris, France; and ††Global Medical Affairs, Pfizer Inc., Groton, Connecticut.
Pediatr Infect Dis J. 2017 Jan;36(1):e1-e13. doi: 10.1097/INF.0000000000001339.
Data on safety and efficacy of voriconazole for invasive aspergillosis (IA) and invasive candidiasis/esophageal candidiasis (IC/EC) in pediatric patients are limited.
Patients aged 2-<18 years with IA and IC/EC were enrolled in 2 prospective open-label, non-comparative studies of voriconazole. Patients followed dosing regimens based on age, weight and indication, with adjustments permitted. Treatment duration was 6-12 weeks for IA patients, ≥14 days after last positive Candida culture for IC patients and ≥7 days after signs/symptoms resolution for EC patients. Primary analysis for both the studies was safety and tolerability of voriconazole. Secondary end points included global response success at week 6 and end of treatment (EOT), all-causality mortality and time to death. Voriconazole exposure-response relationship was explored.
Of 53 voriconazole-treated pediatric patients (31 IA; 22 IC/EC), 14 had proven/probable IA, 7 had confirmed IC and 10 had confirmed EC. Treatment-related hepatic and visual adverse events, respectively, were reported in 22.6% and 16.1% of IA patients, and 22.7% and 27.3% of IC/EC patients. All-causality mortality in IA patients was 14.3% at week 6; no deaths were attributed to voriconazole. No deaths were reported for IC/EC patients. Global response success rate was 64.3% (week 6 and EOT) in IA patients and 76.5% (EOT) in IC/EC patients. There was no association between voriconazole exposure and efficacy; however, a slight positive association between voriconazole exposure and hepatic adverse events was established.
Safety and efficacy outcomes in pediatric patients with IA and IC/EC were consistent with previous findings in adult patients.
伏立康唑用于儿科患者侵袭性曲霉病（IA）及侵袭性念珠菌病/食管念珠菌病（IC/EC）的安全性和有效性数据有限。
年龄在2至未满18岁的IA和IC/EC患者纳入两项伏立康唑前瞻性开放标签、非对照研究。患者根据年龄、体重和适应证遵循给药方案，并允许调整。IA患者的治疗持续时间为6至12周，IC患者在最后一次念珠菌培养呈阳性后≥14天，EC患者在症状/体征缓解后≥7天。两项研究的主要分析均为伏立康唑的安全性和耐受性。次要终点包括第6周和治疗结束时（EOT）的总体反应成功率、全因死亡率和死亡时间。探索了伏立康唑暴露-反应关系。
在53例接受伏立康唑治疗的儿科患者中（31例IA；22例IC/EC），14例确诊/疑似IA，7例确诊IC，10例确诊EC。IA患者中分别有22.6%和16.1%报告了与治疗相关的肝脏和视觉不良事件，IC/EC患者中分别为22.7%和27.3%。IA患者在第6周时的全因死亡率为14.3%；无死亡归因于伏立康唑。IC/EC患者未报告死亡。IA患者的总体反应成功率在第6周和EOT时为64.3%，IC/EC患者在EOT时为76.5%。伏立康唑暴露与疗效之间无关联；然而，伏立康唑暴露与肝脏不良事件之间建立了轻微的正相关。
IA和IC/EC儿科患者的安全性和有效性结果与成人患者先前的研究结果一致。
