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

Authors

  • Christopher C Blyth,

    Corresponding author
    1. School of Paediatrics and Child Health, University of Western Australia
    2. Department of Paediatric and Adolescent Medicine and PathWest Laboratory Medicine, Princess Margaret Hospital for Children, Subiaco, Western Australia
      Dr Christopher Blyth, School of Paediatrics and Child Health, University of Western Australia, Princess Margaret Hospital for Children, Roberts Road, Subiaco, WA 6840, Australia, Fax: +618 9388 2097; email: christopher.blyth@uwa.edu.au
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  • Federica Barzi,

    1. George Institute for Global Health, University of Sydney
    2. Children's Hospital at Westmead, Westmead
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  • Katherine Hale,

    1. Children's Hospital at Westmead, Westmead
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  • David Isaacs

    1. Children's Hospital at Westmead, Westmead
    2. University of Sydney, Sydney, New South Wales, Australia
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  • Conflict of interest: Dr Blyth is a member of the Australian and New Zealand Mycology Interest Group which receives grant support from Gilead Science, Pfizer and Merck Sharp & Dohme. Dr Blyth has received investigator-initiated funds for other research projects from Pfizer and Merck Sharp & Dohme. Dr Hale has received investigator-initiated research funding from Gilead Sciences and Pfizer for other research projects.

Dr Christopher Blyth, School of Paediatrics and Child Health, University of Western Australia, Princess Margaret Hospital for Children, Roberts Road, Subiaco, WA 6840, Australia, Fax: +618 9388 2097; email: christopher.blyth@uwa.edu.au

Abstract

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 0.15–0.89). 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)

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.

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