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Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants

  1. Nicola Austin1,*,
  2. Brian A Darlow2,
  3. William McGuire3

Editorial Group: Cochrane Neonatal Group

Published Online: 28 MAR 2013

Assessed as up-to-date: 31 DEC 2012

DOI: 10.1002/14651858.CD003478.pub4

How to Cite

Austin N, Darlow BA, McGuire W. Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD003478. DOI: 10.1002/14651858.CD003478.pub4.

Author Information

  1. 1

    Christchurch Womens Hospital, NICU, Christchurch, New Zealand

  2. 2

    Christchurch School of Medicine, Department of Paediatrics, CHRISTCHURCH, New Zealand

  3. 3

    Hull York Medical School & Centre for Reviews and Dissemination, University of York, York, Y010 5DD, UK

*Nicola Austin, NICU, Christchurch Womens Hospital, Christchurch, New Zealand. nicola.austin@cdhb.govt.nz.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 MAR 2013

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary

Background

Invasive fungal infection is an important cause of mortality and morbidity in very preterm or very low birth weight infants. Uncertainty exists about the effect of prophylactic oral/topical non-absorbed antifungals to reduce mucocutaneous colonisation and so limit the risk of invasive fungal infection in this population.

Objectives

To assess the effect of prophylactic oral/topical non-absorbed antifungal therapy on the incidence of invasive fungal infection, mortality and morbidity in very preterm or very low birth weight infants.

Search methods

We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library, 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to August 2012), conference proceedings, and previous reviews.

Selection criteria

Randomised controlled trials or quasi-randomised controlled trials that compared the effect of prophylactic oral/topical non-absorbed antifungal therapy versus placebo or no drug or another antifungal agent or dose regimen in very preterm or very low birth weight infants.

Data collection and analysis

We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors.

Main results

Four trials, in which a total of 1800 infants participated, compared oral/topical non-absorbed antifungal prophylaxis (nystatin or miconazole) with placebo or no drug. These trials had various methodological weaknesses including quasi-randomisation, lack of allocation concealment, and lack of blinding of intervention and outcomes assessment. The incidence of invasive fungal infection was very high in the control groups of three of these trials. Meta-analysis found a statistically significant reduction in the incidence of invasive fungal infection [typical risk ratio 0.20 (95% confidence interval 0.14 to 0.27); risk difference -0.18 (-0.21 to -0.16)] but substantial statistical heterogeneity was present. We did not find a statistically significant effect on mortality [typical risk ratio 0.87 (0.72 to 1.05); risk difference -0.03 (-0.06 to 0.01)]. None of the trials assessed posthospital discharge outcomes.

Two trials (N = 265) assessed the effect of oral/topical non-absorbed versus systemic antifungal prophylaxis. Meta-analyses did not find any statistically significant differences in the incidences of invasive fungal infection or all-cause mortality.

Authors' conclusions

The finding of a reduction in risk of invasive fungal infection in very low birth weight infants treated with oral/topical non-absorbed antifungal prophylaxis should be interpreted cautiously because of methodological weaknesses in the included trials. Further large randomised controlled trials in current neonatal practice settings are needed to resolve this uncertainty. These trials might compare oral/topical non-absorbed antifungal agents with placebo, with each other, or with systemic antifungal agents and should include an assessment of effect on long-term neurodevelopmental outcomes.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary

Prophylactic oral/topical non-absorbed antifungal agents to prevent invasive fungal infection in very low birth weight infants

Fungi such as candida (the organism that causes thrush) can cause severe infections in very low birth weight infants (birth weight < 1.5 kg). These infections are often difficult to diagnose and frequently cause death or disability. Therefore, it may be appropriate to attempt to prevent such infections by giving very low birth weight infants antifungal drugs as a routine part of their care. This review assessed specifically the effect of giving infants antifungal drugs that reduce skin and gut carriage of fungi to minimise the chances of a severe infection developing. The trials that were identified suggested that this treatment might reduce severe infection rates but there was no evidence that death rates were reduced. Larger and higher quality trials are needed to resolve this uncertainty.