Intermittent micafungin dosing schedule in pediatric oncology patients ‐ safe for outpatient parenteral antimicrobial therapy?

Jade A. Fox , Nicolette Graham , Rachael Lawson , Sonya Stacey , Julia E. Clark
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Abstract

Introduction

Antifungal prophylaxis is an important preventative strategy for high-risk pediatric oncology patients. When triazoles are contraindicated, micafungin is an alternative to polyenes, due to improved tolerability and limited drug-drug interactions. An intermittent dosing schedule is advantageous for outpatient parenteral antimicrobial therapy (OPAT), but studies assessing safety in pediatric patients are limited.

Methods

This single-centre, retrospective, observational study compared the safety and tolerability of daily (1 mg/kg) and intermittent (3 mg/kg) dosing of amphotericin B liposomal (AmB) and micafungin in children under 18 years, with high-risk leukemia. Results
Of 51 patients, with 76 individual dosing schedules, hepatoxicity and nephrotoxicity were comparable across all four dosing schedules. Severity of hypokalemia was significantly higher amongst patients receiving AmB (p = 0.041), with higher rates of intravenous electrolyte supplementation required. Infusion-related reactions occurred only in the AmB group (22 %). Intermittent administration and dosing of micafungin was well tolerated, with similar effects on liver function and reduced rates of hypokalemia.

Conclusion

This study supports the positive safety profile of intermittent micafungin compared with AmB and describes successful OPAT implementation. Prospective studies assessing efficacy are needed to validate these findings.
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儿科肿瘤患者的间歇性米卡芬净用药计划--门诊肠外抗菌治疗安全吗?
导言抗真菌预防是儿科肿瘤高危患者的重要预防策略。在禁用三唑类药物的情况下,米卡芬净因其更好的耐受性和有限的药物相互作用,成为多烯类药物的替代品。这项单中心、回顾性、观察性研究比较了18岁以下高危白血病患儿每天(1毫克/千克)和间歇(3毫克/千克)服用两性霉素B脂质体(AmB)和米卡芬净的安全性和耐受性。结果 在 51 名患者的 76 种给药方案中,四种给药方案的肝毒性和肾毒性相当。接受氨溴索治疗的患者低钾血症的严重程度明显更高(p = 0.041),需要静脉补充电解质的比例也更高。输液相关反应仅发生在 AmB 组(22%)。间歇性给药和给药米卡芬净的耐受性良好,对肝功能的影响相似,低钾血症发生率降低。需要对疗效进行前瞻性研究来验证这些发现。
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