Chemoprophylaxis of neonatal fungal infections in very low birthweight infants: efficacy and safety of fluconazole and nystatin

Aim: To review the use of antifungal chemoprophylaxis to prevent neonatal invasive fungal infections (IFI) in very low birthweight infants (VLBW <1500 g). Method: Systematic review of randomised controlled trials. Results: Nine trials were identified (2029 infants), with six comparing fluconazole with placebo/no treatment (840 infants), three comparing nystatin with placebo/no treatment (1200 infants) and two comparing fluconazole and nystatin (257 infants). Prophylactic fluconazole reduced the incidence of IFI in VLBW infants <1500 g to 5.1% compared with 16.0% in infants receiving placebo, relative risk (RR) = 0.36 (95% confidence interval 0.150.89). The mortality was 10.9% and 16.7%, respectively (RR 0.76, 0.541.08). Oral nystatin reduced the incidence of IFI in VLBW infants to 5.3% compared with 28.0% in infants receiving placebo (RR 0.16, 0.110.23). Mortality was 7.5% with nystatin and 10.9% with placebo (RR 0.86, 0.591.26). The incidence of IFI in studies comparing fluconazole and nystatin was 3.6% and 8.0%, respectively (RR 0.54, 0.191.56), and mortality was not significantly different: 4.6% versus 9.8% (RR 0.43, 04.31) Conclusions: Prophylactic fluconazole and oral nystatin are both highly effective in preventing IFI in VLBW infants. Both agents are safe without significant toxicities. Antifungal prophylaxis should therefore be used in all VLBW infants. Given the paucity of data comparing fluconazole with nystatin, the choice of antifungal agent should be influenced by the incidence of IFI, local epidemiology and relative cost.