Meta-analysis Of Fluconazole Prophylaxis For Fungal Infection In Extremely Low Birth Weight Infant

Invasive fungal infection (IFI) is a major cause of morbidity and mortality inextremely low birth weight (birth weight <1000gm) infants. Early diagnosis is notpossible, and treatment is difficult and often delayed. All previous published9meta-analyses for fluconazole prophylaxis for fungal infection are concerned with very lowbirth weight (birth weight <1500gm) infants only. Therefore, assessing whether anti-fungal prophylaxis would be beneficial is essential in ELBW infants. A meta-analysiswas conducted to assess whether prophylactic fluconazole therapy could reduce theincidence of IFI, morbidity and mortality in extremely low birth weight (ELBW)infants. PubMed, MEDLINE, Embase and the Cochrane Library (until December2014) databases were searched. Randomized controlled trials were identified from thePubMed database using specific terms (fluconazole, antifungal prophylaxis,fluconazole prophylaxis, randomized controlled trial, extremely low birth infants) andfilters (human; randomized controlled trial; ELBW infants: birth weight <1000gm).The search outputs were limited with the use of relevant search filters for randomizedclinical trials. Selection criteria: Randomized controlled trials which compared theeffects of systemic fluconazole prophylactic therapy versus placebo or no drug inELBW infants were selected. All participants were ELBW infants at <5days of agewhen admitted to the neonatal intensive care unit with a central vascular line orendotracheal tube.（Assessment of trial quality, data extraction and synthesis of datawere performed using standard methods of the Cochrane Neonatal Review Group.）Using the RevMan analytical software package (RevMan, version5.0, CochraneCollaboration, Oxford, U.K.). Main outcome measures: Incidences of IFI, death priorto hospital discharge, neurodevelopmental impairment, conjugated hyperbilirubinemia(CH), invasive bacterial infection (IBI) and necrotizing enterocolitis (NEC) weremeasured by weighted relative risk (RR). Four eligible randomized controlled trialsenrolling a total of1184ELBW infants were included. All trials compared the effect of intravenous fluconazole prophylactic therapy versus placebo or no drug. IFI wassignificantly lower in the prophylactic fluconazole group: typical RR,0.21[95%confidence interval (CI),0.12to0.39]; typical risk difference,-0.07(95%CI,-0.10to-0.05). Death prior to hospital discharge was significantly decreased in infants takingprophylactic fluconazole: RR,0.82(95%CI,0.65to1.03). The following measureswere not significant between the two groups: neurodevelopmental impairment RR,0.04(95%CI,-0.10to0.17), P=0.60; CH RR,1.85(95%CI,0.27to12.70), P=0.53; incidence of IBI RR,1.02(95%CI,0.86to1.21), P=0.83; NEC RR,0.80(95%CI,0.52to1.23), P=0.31.Conclusion:Intravenous prophylactic fluconazole therapy was effective in preventing theincidence of IFI without any significant difference in mortality prior to hospitaldischarge in ELBW infants. This therapy was safe without short-term or long-termneurodevelopmental impairment and significant toxicities. However, further studiesare warranted to evaluate the potential for additional adverse effects.