Systemic antifungal drugs for invasive fungal infection in preterm infants

Clerihew L, McGuire W

Published Online:

January 21, 2009

Very premature infants are at risk of serious infections of the blood, brain, and kidneys due to fungi such as Candida (the organism that causes thrush). Fungi infections are associated with high death rates and with long term brain damage in very premature infants. A variety of different types of drugs for treating fungal infections are available. However, this systematic review found only very limited evidence (one small trial) to support the use of one type of antifungal drug over another. Until this uncertainty is resolved with new large trials, clinicians will continue to base their choice of antifungal agent on data extrapolated from studies in older children and adults.

Abstract (click to read)

Background:

Invasive fungal infection is an increasingly common cause of mortality and morbidity in preterm infants. In addition to amphotericin B, a variety of newer antifungal drugs and drug preparations are available for treatment. There is a need to assess their relative merits.

Objectives:

In preterm infants with suspected or confirmed invasive fungal infection, does treatment with newer systemic antifungal drugs or drug preparations, versus conventional amphotericin B alone, reduce mortality and adverse neurodevelopmental outcomes?

Search strategy:

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, Issue 3, 2003), MEDLINE (1966 - August 2003), EMBASE (1980 - August 2003), conference proceedings, and previous reviews.

Selection criteria:

Randomised and quasi-randomised control trials comparing one antifungal agent or combination of agents with another in preterm infants with suspected or confirmed invasive fungal infection.

Data collection and analysis:

We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using relative risk and risk difference. The pre-specified outcomes were death prior to hospital discharge, longer term neurodevelopment, and adverse drug reactions resulting in discontinuation of therapy.

Main results:

We identified only one small trial. This study compared the use of fluconazole with amphotericin B (5-Fluorocytosine added if fungal meningitis present). Three of 11 infants who were treated with fluconazole died and four of 10 infants who were treated with amphotericin B died : Relative risk: 0.68 (95% confidence interval 0.20, 2.33), Risk Difference -0.13 (95% confidence interval -0.53, 0.27) There were not any data on longer term outcomes.

Authors' conclusions:

From this one small study there are insufficient data to favour one antifungal agent or combination to reduce mortality and adverse neurodevelopmental outcomes in preterm infants with suspected or confirmed invasive fungal infection. A large randomised controlled trial is required to compare the newer antifungal preparations with conventional amphotericin B. Further research may also determine the relative convenience and cost effectiveness of the available drugs.

This record should be cited as:

Clerihew L, McGuire W. Systemic antifungal drugs for invasive fungal infection in preterm infants. Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD003953. DOI: 10.1002/14651858.CD003953.pub2

Assessed as up to date:

October 23, 2003

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Primary Review Group:

Neonatal Group

Health topics:

Infectious disease > Neonatal infections > Fungal infections

Neonatal care > Neonatal infections > Fungal infections

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Systemic antifungal drugs for invasive fungal infection in preterm infants

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