Efficacy And Safety Of Fluconazole In Prophylaxis Of Invasive Fungal Infections In Very Low Birth Weight Infants

Objective:To assess the efficacy and safety of fluconazole in prophylaxis of invasive fungal infection in very low birth weight infants.Methods:Databases including Pubmed,Embase,Cochrane Library,Wanfang Data,VIP and CNKI from inception to October 31,2018 were searched for RCTs that compared the effect of fluconazole in prophylaxis of invasive fungal infection in very low birth weight infants.The incidence of invasive fungal infection and fungal colonization,death prior to hospital discharge and neurodevelopmental outcomes were considered as the primary outcomes,meanwhile,the emergence of resistance to fluconazole,serious complications and duration of intensive care unit or hospital admission were considered as the secondary outcomes.Jadad scale was used to assess the quality of the included studies.A meta-analysis was conducted with RevMan 5.3 software to sum up the data extracted from the included studies,I~2 test was performed to assess the heterogeneity among the studies.Results:12 studies scored more than 3 points according to Jadad scale were included in the study.Very low birth weight infants with prophylactic fluconazole in intervention group and placebo in control group in 11 studies,while the different dose regime in control group in the other 2 studies.(1)The meta-analysis demonstrated that prophylactic fluconazole reduce the incidence of invasive fungal infection(RR=0.44;95%CI:0.27~0.71,P=0.0009),the incidence of fungal colonization(RR=0.31;95%CI:0.24~0.40,P<0.00001)and the incidence of death prior to hospital discharge(RR=0.74;95%CI:0.58~0.94,P=0.01)in VLBW infants compared with the placebo control group.(2)Between the different dose regime groups,the incidence of invasive fungal infection,fungal colonization and death prior to hospital discharge were not significantly different.(3)No significant differences were found in the neurodevelopmental outcomes and other secondary outcomes.Conclusion:Prophylactic fluconazole reduce the incidence of invasive fungal infection and fungal colonization in VLBW infants,small dose and intermittent administration might have the same efficacy.Further researches are needed to assess the emergence of resistance to fluconazole.