Neofytos Dionysis, Huang Yao-Ting, Cheng Kimberly, Cohen Nina, Perales Miguel-Angel, Barker Juliet, Giralt Sergio, Jakubowski Ann, Papanicolaou Genovefa
Infectious Diseases Service.
Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center Department of Medicine, Weill Medical College of Cornell University, New York, New York.
Clin Infect Dis. 2015 Dec 1;61 Suppl 6(Suppl 6):S652-61. doi: 10.1093/cid/civ818.
The use of mold-active azoles for antifungal prophylaxis after allogeneic stem cell transplantation (SCT) is hindered by adverse events and drug-drug interactions. Higher doses of echinocandins administered intermittently may be an alternative in this setting.
This was a single-center, observational 5-year study to characterize the safety and efficacy of intermittent administration of high-dose intravenous micafungin (≥5 doses of ≥300 mg micafungin 2-3 times weekly) in patients with acute leukemia and allogeneic SCT recipients.
A total of 104 patients (84 allogeneic SCT recipients and 20 patients with leukemia) received intermittent high-dose intravenous micafungin, 83 (79.8%) as prophylaxis. Large variability in the micafungin dosing regimen was observed; 78 (75%) patients received >75% of their course as 300 mg micafungin 3 times weekly. Liver function tests decreased from baseline to end of treatment (EOT; P < .001). Patients with normal baseline liver function (n = 55 [52%]) maintained similar enzyme levels throughout the study. For patients with abnormal baseline liver function (n = 49 [47%]), liver function tests significantly improved from baseline to EOT (P ≤ .005). Duration and/or micafungin dosing algorithms were not associated with liver toxicity at EOT. There were no significant changes in renal function, and infusion-related reactions or deaths were not observed. Five of 83 (6.0%) patients in the prophylaxis group developed a breakthrough fungal infection.
In this largest cohort of patients to date, intermittent administration of high-dose micafungin was well tolerated, without any associated liver or renal function abnormalities, and may be considered an alternative antifungal prophylactic strategy. Prospective studies are needed to further validate these findings.
异基因造血干细胞移植（SCT）后使用具有抗霉菌活性的唑类药物进行抗真菌预防受到不良事件和药物相互作用的阻碍。在此情况下，间歇性给予更高剂量的棘白菌素可能是一种替代方法。
这是一项为期5年的单中心观察性研究，旨在描述急性白血病患者和异基因SCT受者间歇性静脉注射高剂量米卡芬净（每周2 - 3次，≥5剂，每剂≥300 mg米卡芬净）的安全性和有效性。
共有104例患者（84例异基因SCT受者和20例白血病患者）接受了间歇性高剂量静脉注射米卡芬净，其中83例（79.8%）用于预防。观察到米卡芬净给药方案存在很大差异；78例（75%）患者在其疗程的>75%时间内接受每周3次300 mg米卡芬净治疗。肝功能检查从基线到治疗结束（EOT）有所下降（P < 0.001）。基线肝功能正常的患者（n = 55 [52%]）在整个研究过程中酶水平保持相似。对于基线肝功能异常的患者（n = 49 [47%]），肝功能检查从基线到EOT有显著改善（P ≤ 0.005）。疗程持续时间和/或米卡芬净给药算法与EOT时的肝毒性无关。肾功能无显著变化，未观察到与输注相关的反应或死亡。预防组的83例患者中有5例（6.0%）发生了突破性真菌感染。
在迄今为止最大的这组患者中，间歇性给予高剂量米卡芬净耐受性良好，未出现任何相关的肝或肾功能异常，可被视为一种替代的抗真菌预防策略。需要进行前瞻性研究以进一步验证这些发现。
