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

School of Paediatrics and Child Health, University of Western Australia Department of Paediatric and Adolescent Medicine and PathWest Laboratory Medicine, Princess Margaret Hospital for Children, Subiaco, Western Australia George Institute for Global Health, University of Sydney Children's Hospital at Westmead, Westmead University of Sydney, Sydney, New South Wales, Australia.
Journal of Paediatrics and Child Health (Impact Factor: 1.15). 09/2012; 48(9):846-51. DOI: 10.1111/j.1440-1754.2012.02543.x
Source: PubMed


To review the use of antifungal chemoprophylaxis to prevent neonatal invasive fungal infections (IFI) in very low birthweight infants (VLBW <1500 g).

Systematic review of randomised controlled trials.

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 0.15-0.89). The mortality was 10.9% and 16.7%, respectively (RR 0.76, 0.54-1.08). Oral nystatin reduced the incidence of IFI in VLBW infants to 5.3% compared with 28.0% in infants receiving placebo (RR 0.16, 0.11-0.23). Mortality was 7.5% with nystatin and 10.9% with placebo (RR 0.86, 0.59-1.26). The incidence of IFI in studies comparing fluconazole and nystatin was 3.6% and 8.0%, respectively (RR 0.54, 0.19-1.56), and mortality was not significantly different: 4.6% versus 9.8% (RR 0.43, 0-4.31)

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.

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    ABSTRACT: Preterm infants, born with immature innate immunity, are less likely to develop anaphylaxis. Fluconazole prophylaxis during the first six weeks of life decreases invasive candidiasis in very low birth weight infants. Adverse effects of fluconazole are very rare. In this study, we report a newborn (a male, 26 weeks gestation and 900 g birth weight) who developed anaphylaxis after fluconazole administration. Hypotension and erythematous rash were present. We believe this to be the first anaphylaxis case in newborns caused by fluconazole in literature. Clinicians should be aware of the possibility of this potentially fatal adverse effect occurring with intravenous fluconazole.
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    ABSTRACT: Background: Premature infants are at high risk of developing invasive candidal infections (ICI). We investigated maternal and perinatal risk factors for ICI that may help in defining at-risk infants, allowing more targeted antifungal prophylaxis to prevent morbidity and mortality. Methods: Maternal and neonatal data from infants with a birthweight between 500 and 1250 g admitted across 95 neonatal intenisve care units were analyzed for risk factors for ICI. Results: Data from 1890 infants were analyzed, 78 of whom had ICI. Overall mortality was 20.5% for all cases of ICI, 18.8% with candidemia, 17.2% with candiduria, and 75% when Candida was isolated in both the blood and urine. Birthweight, gestational age, male sex, and vaginal delivery were predictors of infection on univariate analysis. After logistic regression, gestational age (P < .01) and male sex (P < .01) remained significant. Vaginal birth and receiving antibiotics during the first week of life increased the risk for ICI in the 22-25 weeks' and 26-28 weeks' gestation subgroups. Conclusions: Gestational age and male gender are risk factors for the development of ICI, whereas vaginal delivery and antibiotics during the first week further increase the incidence in the more premature infants. Knowing maternal and perinatal risk factors for ICI allows more targeted antifungal prophylaxis in at-risk infants.
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    No preview · Article · Jul 2013 · Expert Review of Anti-infective Therapy
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