OBJECTIVETo evaluate the effect of fluconazole in prophylaxis of fungal infection in very low birth weight infants.

METHODSPubMed, EMBASE, Ovid, China National Knowledge Infrastructure, Vip Chinese Periodical Database, Wanfang Chinese Periodical Database and Chinese Bio-medicine Database were searched for the case-control study on the effect of fluconazole in prophylaxis of fungal infection in very low birth weight infants from Jan. 1994 to Jan. 2009. Articles were evaluated according to inclusion criteria. Poor-quality studies were excluded, and RevMan 4.22 software was applied for investigating the heterogeneity among individual studies and calculating the pooled risk ratio (RR) and 95% confidence interval (CI).

RESULTSFive eligible randomized clinical trials were included. Four studies were graded as "A" and one study was graded "B". Meta-analysis based on the included studies showed that the prophylactic fluconazole could significantly reduce the fungal colonization (RR: 0.32 and 95% CI: 0.23 to 0.44, P < 0.00001); and infections (RR: 0.44 and 95% CI: 0.29 to 0.65, P < 0.0001) in very low birth weight neonates. However, there was no statistically significant difference between the infants treated and not treated with prophylactic fluconazole in the neonatal mortality (RR: 0.68 and 95% CI: 0.43 to 1.07, P = 0.09) and the prophylactic use of fluconazole did not show any side-effects on the liver and bilirubin. None of the studies found any significant changes in the minimal inhibitory concentration of fluconazole in fungal isolates during the study period. There were different results about the emergence of resistance to fluconazole.

CONCLUSIONSMeta-analysis of five randomized controlled trials suggest that prophylactic fluconazole reduces the incidence of fungal colonization and invasive fungal infection in very low birth weight infants. Further trials are needed to provide more precise evaluation on efficacy, and to assess the effect on mortality, neurodevelopment and the emergence of resistance to antifungal agents. Different NICU should have different policy on prophylactic fluconazole and also adjust the policy at different time according to the incidence of fungal infection and antifungal drug resistance.