Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections
Safety and efficacy of high-dose intravenous acyclovir in the management of neonatal herpes simplex virus infections
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DOI：
10.1542/peds.108.2.230
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发表时间：
2001-08-01
期刊：
影响因子：
8
通讯作者：
Whitley, RJ
中科院分区：
文献类型：
--
作者：
Kimberlin, DW;Lin, CY;Whitley, RJ
Objective.本研究的目的是确定大剂量（HD）阿昔洛韦治疗新生儿单纯疱疹病毒（HSV）疾病的安全性。此外，在死亡率和发病率方面，寻求治疗效果的估计。HD阿昔洛韦的病毒学疗效也进行了评估。小于或等于28日龄且认为疾病由HSV引起的婴儿入组本研究。中枢神经系统（CNS; N = 28）或播散性（N = 41）HSV感染患者可参与试验。少数HSV疾病仅限于皮肤、眼睛或口腔的患者（SEM; N = 10）或其疾病在临床上与HSV一致但未进行病毒学感染确认的患者（N = 9）也出于同情而入组。仅病毒学证实的HSV疾病患者纳入疗效分析。所有入选患者均纳入安全性分析。该研究是一项开放标签的静脉注射阿昔洛韦的评价，剂量高于美国食品和药物管理局批准的30 mg/kg/d标准剂量。前16例患者接受中剂量（ID）阿昔洛韦（45 mg/kg/d），接下来的72例患者接受HD阿昔洛韦（60 mg/kg/d）。阿昔洛韦分3次每日给药，共21天。在整个治疗过程中以及出生后前4年的计划随访访视时，对新生儿进行前瞻性评估。将数据与之前的国家过敏和传染病研究所抗病毒协作研究组试验进行比较，在该试验中，患者接受标准剂量（SD）阿昔洛韦治疗10天，并且使用相同的方法（除了阿昔洛韦剂量和治疗持续时间）。6（21%）的29 HD阿昔洛韦接受者的HSV疾病仍然局限于SEM或CNS经历中性粒细胞减少症。6例中有1例中性粒细胞绝对计数
Objective. The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed.Participants. Infants who were less than or equal to 28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses.Methods. The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used.Results. Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count