Division of Pediatric Infectious Diseases, Children's Hospital of Orange County, Orange, California 92868, USA.
Clin Ther. 2010 Feb;32(2):265-71. doi: 10.1016/j.clinthera.2010.02.016.
This study was conducted to evaluate once-weekly liposomal amphotericin B (L-AmB) for Candida prophylaxis in very low birth weight (VLBW) neonates.
This prospective, randomized, open-label, placebo-controlled study included neonates who were <32 weeks' gestational age, <7 days old, and weighing <1500 g at birth. Subjects were randomized to receive L-AmB 5 mg/kg per week or placebo (dextrose water) and were followed until 6 weeks of age. Surveillance cultures were obtained at baseline, at 72 hours, and weekly thereafter. Study drug was continued until 6 weeks after birth or the discontinuation of high-risk treatments and invasive devices, whichever occurred first. Blood cultures were obtained as clinically indicated. The primary end point was development of Candida colonization by 6 weeks' postnatal age; secondary end points included development of invasive candidiasis and occurrence of treatment-related adverse events. Safety variables included renal and hepatic function tests, incidence of grade III-IV intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC), and mortality.
Forty subjects were enrolled and randomized to receive L-AmB (12 males, 8 females; 50% white) or placebo (12 males, 8 females; 35% white). Subjects were evenly distributed by gestational age, age at enrollment, birth weight, race, and sex. Consent was withdrawn after completion of study treatment in 1 subject (L-AmB); 1 subject in each study arm died during the study; and 3 subjects were transferred back to their referring institutions (1 L-AmB, 2 placebo). Thus, 17 subjects in each arm completed all study procedures, although all 40 subjects were evaluable. Colonization before administration of study drug was noted in 4 L-AmB subjects (20%) and 1 placebo subject (5%); 1 (5%) and 3 (15%) subjects in the respective groups developed colonization while receiving study drug. No L-AmB subjects and 1 placebo subject developed candidiasis. One subject in each group died; these deaths were not considered related to study drug or fungal infection. There were no clinical differences between groups in the incidence of grade III-IV IVH, NEC, hypokalemia, nephrotoxicity, need for platelet or packed red blood cell transfusion, or mortality.
L-AmB 5 mg/kg once weekly was generally well tolerated in these VLBW infants. The data did not allow evaluation of efficacy. A larger, multicenter, randomized clinical trial of L-AmB for Candida prophylaxis that is appropriately powered is warranted.
本研究旨在评估每周一次脂质体两性霉素 B（L-AmB）用于极低出生体重（VLBW）新生儿的念珠菌预防。
本前瞻性、随机、开放标签、安慰剂对照研究纳入了胎龄<32 周、<7 天、出生体重<1500 g 的新生儿。受试者随机接受 L-AmB 5 mg/kg/周或安慰剂（葡萄糖水）治疗，并随访至 6 周龄。基线时、72 小时和此后每周进行监测培养。研究药物持续使用至出生后 6 周或高危治疗和有创器械停止使用，以先发生者为准。根据临床指征获取血培养。主要终点为出生后 6 周内念珠菌定植的发展；次要终点包括侵袭性念珠菌病的发生和治疗相关不良事件的发生。安全性变量包括肾功能和肝功能检查、III-IV 级脑室出血（IVH）和坏死性小肠结肠炎（NEC）的发生率以及死亡率。
40 例受试者入组并随机接受 L-AmB（12 名男性，8 名女性；50%为白人）或安慰剂（12 名男性，8 名女性；35%为白人）治疗。受试者在胎龄、入组时的年龄、出生体重、种族和性别方面分布均匀。1 例（L-AmB）受试者在完成研究治疗后撤回同意；每个研究组各有 1 例受试者在研究期间死亡；3 例（1 例 L-AmB，2 例安慰剂）受试者转回其转介机构。因此，每组各有 17 例受试者完成了所有研究程序，尽管所有 40 例受试者均具有可评估性。4 例 L-AmB 受试者（20%）和 1 例安慰剂受试者（5%）在给予研究药物前已存在定植；在接受研究药物时，各组分别有 1 例（5%）和 3 例（15%）受试者发生定植。无 L-AmB 受试者和 1 例安慰剂受试者发生念珠菌病。每组各有 1 例受试者死亡；这些死亡被认为与研究药物或真菌感染无关。两组在 III-IV 级 IVH、NEC、低钾血症、肾毒性、血小板或浓缩红细胞输注的需要以及死亡率方面无临床差异。
每周一次 5 mg/kg L-AmB 在这些极低出生体重儿中通常耐受良好。数据不允许评估疗效。需要进行更大规模、多中心、随机临床试验以评估 L-AmB 用于念珠菌预防的疗效。
