FLUCONAZOLE PROPHYLAXIS FOR THE PREVENTION OF CANDIDIASIS IN INFANTS <750 GRAMS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目的是评估预防氟康唑是否会减少最有可能患念珠菌病的婴儿的死亡率或念珠菌病。这项研究将监测研究药物的安全性，直到死亡或从NICU出院。此外，还将评估存活18-22个月婴儿的神经发育情况。这项试验的多中心性质将有助于控制不同中心之间由于不同护理实践而导致的念珠菌病发病率的变异性。总研究时间为3年--入学为18个月，神经发育随访为18个月。 氟康唑预防将减少那些最有可能患念珠菌病的婴儿的死亡或念珠菌病。 目的1：确定氟康唑能否预防早产儿的死亡或念珠菌病假设1：预防氟康唑将使出生体重小于750克的新生儿的死亡或念珠菌病的发生率绝对降低15%。 目的2：确定氟康唑预防对神经发育障碍的影响假设2：氟康唑预防将改善18-22个月校正年龄的幸存者的神经发育结果 目的3：确定氟康唑假说的安全性和药代动力学3：氟康唑剂量为6 mg/kg，每周两次，是安全和合适的剂量。 目的：评估氟康唑预防对真菌的耐药性假说4：接受安慰剂和氟康唑的婴儿分离株的MIC没有差异。 目的5：收集清除的血液样本，用于研究发生念珠菌感染的婴儿和没有发生念珠菌感染的婴儿之间的遗传变异。假设5：与没有发生念珠菌感染的婴儿相比，发生念珠菌感染的婴儿将表现出遗传变异。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study is designed to assess whether fluconazole prophylaxis will decrease death or candidiasis among infants most at risk for candidiasis, those <750g. This study will monitor for safety while on study drug until death or discharge from the NICU. In addition neurodevelopment will be assessed in the surviving infants at 18-22 months. The multi-center nature of this trial will help control for variability in rates of candidiasis between centers due to different care practices. Total study time will be 3 years--18 months for enrollment and 18 months corrected age for neurodevelopmental follow-up. Floconazole prophylaxis will decrease death or candidiasis among infants most at risk for candidiasis, those <750g. AIM 1: Determine if fluconazole prevents death or candidiasis in premature infants Hypothesis 1: Fluconazole prophylaxis will result in an absolute reduction of 15% in death or candidiasis in neonates born less than 750g. AIM 2: Determine effect of fluconazole prophylaxis on neurodevelopmental impairment Hypothesis 2: Fluconazole prophylaxis will result in improved neurodevelopmental outcomes in survivors at 18-22 months corrected age AIM 3: Determine the safety and pharmacokinetics of fluconazole Hypothesis 3: A fluconazole dose of 6 mg/kg twice weekly will be a safe and appropriate dosage. AIM 4: Evaluate antifungal resistance due to fluconazole prophylaxis Hypothesis 4: There will be no difference in MIC between isolates from infants receiving placebo and fluconazole. AIM 5: Collect scavenged blood sample for studies of associations between genetic variation in infants who develop Candida infections and those who don t. Hypothesis 5: Infant who develop Candida infections will exhibit genetic variation when compared to infant who do not develop Candida infections.