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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 本研究旨在评估氟康唑预防是否会降低最有念珠菌病风险的婴儿（<750 g）的死亡或念珠菌病。本研究将监测研究药物期间的安全性，直至死亡或从NICU出院。此外，将在18-22个月时评估存活婴儿的神经发育。本试验的多中心性质将有助于控制由于不同护理实践导致的各中心之间念珠菌病发生率的差异。总研究时间为3年--入组18个月，神经发育随访校正年龄为18个月。 氟康唑预防将减少死亡或念珠菌感染的婴儿最危险的念珠菌病，那些<750克。 目标1：确定氟康唑是否可预防早产儿死亡或念珠菌病假设1：氟康唑预防将导致出生时体重小于750 g的新生儿死亡或念珠菌病绝对减少15%。 目标2：确定氟康唑预防治疗对神经发育障碍的影响假设2：氟康唑预防治疗将改善18-22个月矫正年龄存活者的神经发育结局 目标3：确定氟康唑的安全性和药代动力学假设3：氟康唑剂量为6 mg/kg，每周两次，将是安全和适当的剂量。 目标4：评估氟康唑预防治疗引起的抗真菌药耐药性假设4：接受安慰剂和氟康唑治疗的婴儿分离株的MIC没有差异。 目标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未发生念珠菌感染的婴儿的遗传变异之间的关联。假设5：与未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.