Austin N C, Darlow B
Neonatal Intensive Care Unit, Christchurch Women's Hospital, Christchurch, New Zealand, Private Bag 4711, Christchurch, New Zealand.
Cochrane Database Syst Rev. 2004(1):CD003478. doi: 10.1002/14651858.CD003478.pub2.
Systemic fungal infection has increased in prevalence in neonatal intensive care units (NICU) caring for very low birth weight infants. It is associated with a prolonged stay and an increase in morbidity and mortality. An assessment of the use of oral prophylactic antifungals to prevent systemic infection is needed.
To assess whether the prophylactic administration of oral antifungal agents to very preterm infants reduces the occurrence of systemic fungal infection.
The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Searches were carried out up to July 2003 on the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 2, 2003), MEDLINE from 1966, EMBASE from 1980, CINAHL from 1992. Abstracts from SPR (1993 - 2003) and ESPR (1995 to 2002) were hand searched.
Randomized and quasi randomized controlled trials in very low birth weight or very preterm infants in which an oral antifungal agent was compared with placebo or no treatment or another oral antifungal agent
Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of the trial quality and data extraction undertaken by each author. Results were reported using relative risk (RR) and risk difference (RD) and weighted mean difference (WMD). 95% confidence intervals were reported.
We identified three eligible trials, one comparing nystatin with no treatment (67 infants), one comparing miconazole with placebo (600 infants), and one comparing nystatin with fluconazole (21 infants). As the two trials comparing nystatin or miconazole with placebo or no treatment were clinically quite different, meta-analysis was not performed. In the trial of nystatin versus no treatment, systemic fungal infection was significantly reduced [RR 0.19 (0.04,0.78)] in the group treated with nystatin. In the study comparing miconazole with placebo there was no significant effect on systemic fungal infection [RR 1.32 (0.46,3.75)]. Neither study found a significant effect on mortality, and there was no significant difference in the mean number of days infants received ventilation or stayed in the neonatal intensive care unit. In the small trial comparing oral fluconazole with nystatin, no significant difference in systemic fungal infection [RR 0.17 (0.01, 2.84)] or mortality [RR 0.17 (0.01, 2.84)] was reported. Adverse drug reactions were not reported in any study.
REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of prophylactic oral antifungal agents in very low birth weight infants in the neonatal intensive care unit. Randomised controlled trials in current neonatal practice settings are needed, comparing oral antifungal agents with placebo and with each other and including an assessment of side effects, in order to determine whether oral antifungal agents have a role in preventing systemic fungal infections in preterm infants.
在照顾极低出生体重儿的新生儿重症监护病房（NICU）中，系统性真菌感染的患病率有所上升。它与住院时间延长以及发病率和死亡率增加有关。需要评估口服预防性抗真菌药物预防系统性感染的使用情况。
评估对极早产儿预防性给予口服抗真菌药物是否能降低系统性真菌感染的发生率。
采用Cochrane协作网及其新生儿回顾小组的标准方法。截至2003年7月，检索了Cochrane对照试验中央注册库（CENTRAL，Cochrane图书馆2003年第2期）、1966年以来的MEDLINE、1980年以来的EMBASE、1992年以来的CINAHL。手工检索了SPR（1993 - 2003年）和ESPR（1995年至2002年）的摘要。
对极低出生体重或极早产儿进行的随机和半随机对照试验，其中将口服抗真菌药物与安慰剂、无治疗或另一种口服抗真菌药物进行比较
采用Cochrane新生儿回顾小组的标准方法提取数据，每位作者分别对试验质量和数据提取进行评估。结果以相对风险（RR）、风险差异（RD）和加权平均差异（WMD）报告，并报告95%置信区间。
我们确定了三项符合条件的试验，一项将制霉菌素与无治疗进行比较（67例婴儿），一项将咪康唑与安慰剂进行比较（600例婴儿），一项将制霉菌素与氟康唑进行比较（21例婴儿）。由于将制霉菌素或咪康唑与安慰剂或无治疗进行比较的两项试验在临床上差异较大，未进行荟萃分析。在制霉菌素与无治疗的试验中，可以看到制霉菌素治疗组的系统性真菌感染显著减少[RR 0.19（0.04，0.78）]。在将咪康唑与安慰剂进行比较的研究中，对系统性真菌感染没有显著影响[RR 1.32（0.46，3.75）]。两项研究均未发现对死亡率有显著影响，婴儿接受通气的平均天数或在新生儿重症监护病房停留的时间也没有显著差异。在比较口服氟康唑与制霉菌素的小型试验中，未报告系统性真菌感染[RR 0.17（0.01，2.84）]或死亡率[RR 0.17（0.01，2.84）]有显著差异。任何研究均未报告药物不良反应。
没有足够的证据支持在新生儿重症监护病房对极低出生体重儿使用预防性口服抗真菌药物。需要在当前的新生儿实践环境中进行随机对照试验，将口服抗真菌药物与安慰剂相互比较，并评估副作用，以确定口服抗真菌药物在预防早产儿系统性真菌感染方面是否有作用。
