McGuire W, Clerihew L, Austin N
Tayside Institute of Child Health, Ninewells Hospital and Medical School, Dundee, UK, DD1 9SY.
Cochrane Database Syst Rev. 2004(1):CD003850. doi: 10.1002/14651858.CD003850.pub2.
Invasive fungal infection is an increasingly common cause of mortality and morbidity in very low birth weight infants. As the diagnosis is often difficult, and treatment is often delayed, there is a need to assess whether antifungal prophylaxis is beneficial.
To assess whether prophylactic intravenous antifungal therapy reduces mortality and adverse neurodevelopmental outcomes in very low birth weight infants.
We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2003), MEDLINE (1966 - October 2003), EMBASE (1980 - October 2003), conference proceedings, and previous reviews.
Randomised controlled trials that compared the effect of prophylactic intravenous antifungal therapy versus placebo, or no drug, or another antifungal agent, in very low birth weight infants.
We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using relative risk and risk difference. The pre-specified outcomes were death prior to hospital discharge, longer term neurodevelopment, incidence of invasive fungal infection, emergence of antifungal resistance, and adverse drug reactions.
We identified three eligible trials enrolling a total of 214 infants. Each of the trials compared the effect of prophylactic intravenous fluconazole versus placebo. Two of the trials reported death prior to hospital discharge as an outcome. 29 of the 203 infants recruited to these studies died. Meta-analysis revealed a statistically significantly reduced risk of death prior to hospital discharge for the infants who received fluconazole prophylaxis: typical relative risk: 0.44 (95% confidence interval 0.21, 0.91); typical risk difference: -0.11 (95% confidence interval -0.21, -0.02); number needed to treat: 9 (95% confidence interval 5, 50). None of the trials reported data on longer term outcomes.
REVIEWER'S CONCLUSIONS: We have found some evidence that prophylactic intravenous fluconazole reduces mortality prior to hospital discharge in very low birth weight infants. The meta-analysis suggests that there will be one fewer death in every nine infants treated with this intervention, but the 95% confidence interval around this estimate of effect is wide. The longer term neurodevelopmental consequences for infants exposed to this intervention remain to be determined. It will be important to identify any subgroups of very low birth weight infants that receive the most benefit from this intervention. There is also a need for further data on the effect of the intervention on the emergence of organisms with stable antifungal resistance.
侵袭性真菌感染是极低出生体重儿死亡和发病的一个日益常见的原因。由于诊断往往困难，且治疗常常延迟，因此有必要评估抗真菌预防是否有益。
评估预防性静脉内抗真菌治疗是否能降低极低出生体重儿的死亡率和不良神经发育结局。
我们采用了Cochrane新生儿综述小组的标准检索策略。这包括检索Cochrane对照试验中心注册库（CENTRAL，《Cochrane图书馆》，2003年第4期）、MEDLINE（1966年至2003年10月）、EMBASE（1980年至2003年10月）、会议论文集以及以往的综述。
比较预防性静脉内抗真菌治疗与安慰剂、或不使用药物、或另一种抗真菌药物对极低出生体重儿影响的随机对照试验。
我们使用Cochrane新生儿综述小组的标准方法提取数据，每位作者分别评估试验质量和数据提取情况，并使用相对风险和风险差进行数据综合分析。预先设定的结局包括出院前死亡、长期神经发育、侵袭性真菌感染的发生率、抗真菌耐药性的出现以及药物不良反应。
我们确定了三项符合条件的试验，共纳入214名婴儿。每项试验都比较了预防性静脉内氟康唑与安慰剂的效果。其中两项试验将出院前死亡作为一项结局进行了报告。纳入这些研究的203名婴儿中有29名死亡。荟萃分析显示，接受氟康唑预防的婴儿出院前死亡风险在统计学上显著降低：典型相对风险为0.44（95%置信区间0.21，0.91）；典型风险差为-0.11（95%置信区间-0.21，-0.02）；需治疗人数为9（95%置信区间5，50）。没有一项试验报告长期结局的数据。
我们发现一些证据表明，预防性静脉内氟康唑可降低极低出生体重儿出院前的死亡率。荟萃分析表明，接受这种干预措施治疗的每九名婴儿中预计可减少一例死亡，但该效应估计值的95%置信区间较宽。暴露于这种干预措施的婴儿的长期神经发育后果仍有待确定。确定从这种干预措施中获益最大的极低出生体重儿亚组非常重要。还需要进一步的数据来了解该干预措施对具有稳定抗真菌耐药性的生物体出现的影响。
