Systemic antifungal drugs for invasive fungal infection in preterm infants

Preterm and sick newborn infants are at risk of serious infections of the blood, brain and kidneys due to fungi such as Candida (the organism that causes thrush). Severe fungal infections are associated with high death rates and with long-term brain damage in newborn 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 may continue to base their choice of antifungal agent on data extrapolated from studies in older children and adults.

Authors' conclusions: 

There are insufficient data to inform practice. Large randomised controlled trials are required to compare antifungal drugs, drug preparations or drug combinations for treating newborn infants with invasive fungal infection.

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Background: 

A variety of antifungal drugs, drug preparations and drug combinations are available to treat newborn infants with suspected or confirmed invasive fungal infection. There is a need to assess their relative merits.

Objectives: 

To assess the effect of treatment with different antifungal drugs, drug preparations or drug combinations on mortality and morbidity in newborn infants with suspected or confirmed invasive fungal infection.

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 (The Cochrane Library, 2012, Issue 2), MEDLINE, EMBASE, CINAHL (to March 2012), conference proceedings and previous reviews.

Selection criteria: 

Randomised and quasi-randomised control trials comparing one antifungal agent or combination of agents with another in newborn 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 risk ratio and risk difference.

Main results: 

We identified only one small trial in which 24 newborn infants participated. This trial compared the use of fluconazole versus amphotericin B (plus 5-fluorocytosine if fungal meningitis present). The trial did not detect a statistically significant effect on mortality (risk ratio 0.73; 95% confidence interval 0.26 to 2.05).

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